Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 9.129
Filtrar
1.
Sheng Li Xue Bao ; 71(4): 625-636, 2019 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-31440760

RESUMO

Mitochondrial dynamics, involving mitochondrial fusion, fission and autophagy, plays an important role in maintaining cellular physiological function and homeostasis. Mitochondria are the "energy plant" of human body, so the changes of mitochondrial fusion, division and autophagy are important for cell respiration and energy production. On the other hand, energy metabolism influences mitochondrial dynamics in turn. This paper reviewed the recent advances in studies on the relationship between energy metabolism and the proteins regulating mitochondrial fusion, fission and autophagy. The association of mitochondrial dynamics with electron chain complex expression, oxidative phosphorylation and ATP synthesis upon exercise intervention will provide theoretical references for the further studies in sports training and disease intervention.


Assuntos
Autofagia , Metabolismo Energético , Exercício , Mitocôndrias/fisiologia , Dinâmica Mitocondrial , Trifosfato de Adenosina/biossíntese , Humanos , Proteínas Mitocondriais/metabolismo
2.
Adv Exp Med Biol ; 1158: 17-44, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31452133

RESUMO

Parkinson's disease (PD) is a multifactorial disorder whose etiology is not completely understood. Strong evidences suggest that mitochondrial impairment and altered mitochondrial disposal play a key role in the development of this pathology. Here we show this association in both genetic and sporadic forms of the disease. Moreover, we describe the mitochondrial dysfunctions in toxin-induced models of PD, thus highlighting the importance of environmental factors in the onset of this pathology. In particular, we focus our attention on mitochondrial dynamics, mitochondrial biogenesis, and mitophagy and explain how their impairment could have a negative impact on dopaminergic neurons function and survival. Lastly, we aim at clarifying the important role played by proteomics in this field of research, proteomics being a global and unbiased approach suitable to unravel alterations of the molecular pathways in multifactorial diseases.


Assuntos
Proteínas Mitocondriais , Doença de Parkinson , Neurônios Dopaminérgicos/patologia , Humanos , Mitocôndrias/metabolismo , Degradação Mitocondrial , Proteínas Mitocondriais/metabolismo , Doença de Parkinson/fisiopatologia
3.
Adv Exp Med Biol ; 1158: 59-70, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31452135

RESUMO

Mitochondria have a central role in cellular metabolism and reversible post-translational modifications regulate activity of mitochondrial proteins. Thanks to advances in proteomics, lysine acetylation has arisen as an important post-translational modification in the mitochondrion. During acetylation an acetyl group is covalently attached to the epsilon amino group in the side chain of lysine residues using acetyl-CoA as the substrate donor. Therefore the positive charge is neutralized, and this can affect the function of proteins thereby regulating enzyme activity, protein interactions, and protein stability. The major deacetylase in mitochondria is SIRT3 whose activity regulates many mitochondrial enzymes. The method of choice for the analysis of acetylated proteins foresees the combination of mass spectrometry-based proteomics with affinity enrichment techniques. Beyond the identification of lysine-acetylated proteins, many studies are moving towards the characterization of acetylated patterns in different diseases. Indeed, modifications in lysine acetylation status can directly alter mitochondrial function and, therefore, be linked to human diseases such as metabolic diseases, cancer, myocardial injury and neurodegenerative diseases. Despite the progress in the characterization of different lysine acetylation sites, additional studies are needed to differentiate the specific changes with a significant biological relevance.


Assuntos
Lisina , Mitocôndrias , Fenótipo , Acetilação , Humanos , Lisina/metabolismo , Mitocôndrias/química , Mitocôndrias/metabolismo , Proteínas Mitocondriais/química , Proteínas Mitocondriais/metabolismo , Processamento de Proteína Pós-Traducional
4.
Adv Exp Med Biol ; 1158: 119-142, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31452139

RESUMO

The mitochondrion is a vital organelle that performs diverse cellular functions. In this regard, the cell has evolved various mechanisms dedicated to the maintenance of the mitochondrial proteome. Among them, AAA+ ATPase-associated proteases (AAA+ proteases) such as the Lon protease (LonP1), ClpXP complex, and the membrane-bound i-AAA, m-AAA and paraplegin facilitate the clearance of misfolded mitochondrial proteins to prevent the accumulation of cytotoxic protein aggregates. Furthermore, these proteases have additional regulatory functions in multiple biological processes that include amino acid metabolism, mitochondria DNA transcription, metabolite and cofactor biosynthesis, maturation and turnover of specific respiratory and metabolic proteins, and modulation of apoptosis, among others. In cancer cells, the increase in intracellular ROS levels promotes tumorigenic phenotypes and increases the frequency of protein oxidation and misfolding, which is compensated by the increased expression of specific AAA+ proteases as part of the adaptation mechanism. The targeting of AAA+ proteases has led to the discovery and development of novel anti-cancer compounds. Here, we provide an overview of the molecular characteristics and functions of the major mitochondrial AAA+ proteases and summarize recent research efforts in the development of compounds that target these proteases.


Assuntos
Proteínas Mitocondriais , ATPases Associadas a Diversas Atividades Celulares/metabolismo , Ativação Enzimática , Humanos , Mitocôndrias/metabolismo , Proteínas Mitocondriais/metabolismo , Neoplasias/enzimologia , Neoplasias/fisiopatologia , Neoplasias/terapia , Protease La/metabolismo
5.
Adv Exp Med Biol ; 1158: 183-196, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31452141

RESUMO

The term 'mitochondrial dynamics' is commonly used to refer to ongoing fusion and fission of mitochondrial structures within a living cell. A growing number of diseases, from Charcot Marie Tooth Type 2a neuropathies to cancer, is known to be associated with the dysregulation of mitochondrial dynamics, leading to irregularities of mitochondrial network morphology that are associated with aberrant metabolism and cellular dysfunction. Studying these phenomena, and potential pharmacological interventions to correct them, in cultured cells is a powerful approach to developing treatments or cures. Appropriately designed experiments and quantitative approaches for characterizing mitochondrial morphology and function are essential for furthering our understanding. In this chapter, we discuss the importance of cell incubation conditions, choices around imaging modalities, and data analysis tools with respect to experimental outcomes and the interpretation of results from studies of mitochondrial dynamics. We focus primarily on the quantitative analysis of mitochondrial morphology, providing an overview of the available tools and approaches currently being used and discussing some of the strengths and weaknesses associated with each. Finally, we discuss how the ongoing development of imaging and analysis tools continues to improve our ability to study normal and aberrant mitochondrial physiology in vitro and in vivo.


Assuntos
Mitocôndrias , Dinâmica Mitocondrial , Proteínas Mitocondriais , Técnicas de Cultura de Células , Linhagem Celular , Doença de Charcot-Marie-Tooth/fisiopatologia , Humanos , Mitocôndrias/patologia , Mitocôndrias/fisiologia , Dinâmica Mitocondrial/fisiologia , Proteínas Mitocondriais/metabolismo , Neoplasias/fisiopatologia
6.
Nature ; 571(7765): 429-433, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31292547

RESUMO

Balanced fusion and fission are key for the proper function and physiology of mitochondria1,2. Remodelling of the mitochondrial inner membrane is mediated by the dynamin-like protein mitochondrial genome maintenance 1 (Mgm1) in fungi or the related protein optic atrophy 1 (OPA1) in animals3-5. Mgm1 is required for the preservation of mitochondrial DNA in yeast6, whereas mutations in the OPA1 gene in humans are a common cause of autosomal dominant optic atrophy-a genetic disorder that affects the optic nerve7,8. Mgm1 and OPA1 are present in mitochondria as a membrane-integral long form and a short form that is soluble in the intermembrane space. Yeast strains that express temperature-sensitive mutants of Mgm19,10 or mammalian cells that lack OPA1 display fragmented mitochondria11,12, which suggests that Mgm1 and OPA1 have an important role in inner-membrane fusion. Consistently, only the mitochondrial outer membrane-not the inner membrane-fuses in the absence of functional Mgm113. Mgm1 and OPA1 have also been shown to maintain proper cristae architecture10,14; for example, OPA1 prevents the release of pro-apoptotic factors by tightening crista junctions15. Finally, the short form of OPA1 localizes to mitochondrial constriction sites, where it presumably promotes mitochondrial fission16. How Mgm1 and OPA1 perform their diverse functions in membrane fusion, scission and cristae organization is at present unknown. Here we present crystal and electron cryo-tomography structures of Mgm1 from Chaetomium thermophilum. Mgm1 consists of a GTPase (G) domain, a bundle signalling element domain, a stalk, and a paddle domain that contains a membrane-binding site. Biochemical and cell-based experiments demonstrate that the Mgm1 stalk mediates the assembly of bent tetramers into helical filaments. Electron cryo-tomography studies of Mgm1-decorated lipid tubes and fluorescence microscopy experiments on reconstituted membrane tubes indicate how the tetramers assemble on positively or negatively curved membranes. Our findings convey how Mgm1 and OPA1 filaments dynamically remodel the mitochondrial inner membrane.


Assuntos
Chaetomium/química , Microscopia Crioeletrônica , Proteínas Fúngicas/química , Proteínas Fúngicas/metabolismo , Proteínas de Ligação ao GTP/química , Membranas Mitocondriais/metabolismo , Proteínas Mitocondriais/química , Cristalografia por Raios X , Proteínas Fúngicas/ultraestrutura , Proteínas de Ligação ao GTP/metabolismo , Proteínas de Ligação ao GTP/ultraestrutura , Galactosilceramidas/metabolismo , Proteínas Mitocondriais/metabolismo , Proteínas Mitocondriais/ultraestrutura , Modelos Moleculares , Domínios Proteicos , Multimerização Proteica
7.
J Agric Food Chem ; 67(30): 8312-8318, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31287303

RESUMO

The role of inositol 1,4,5-trisphosphate (IP3) in nitric oxide (NO)-reduced chilling injury (CI) in peach fruit was investigated. The fruit were immersed in sodium nitroprusside (SNP) (NO donor) and neomycin (IP3 inhibitor). Results showed that chilling tolerance was enhanced upon exogenous SNP in postharvest peach fruit. Further, GABA accumulation was stimulated by SNP. The increase in protein expression and activity for enzymes in GABA biosynthesis, including glutamate decarboxylase (GAD), polyamine oxidase (PAO), and amino aldehyde dehydrogenase (AMADH), upon SNP treatment was also observed. Also, the up-regulation of Δ1-pyrroline-5-carboxylate synthetase (P5CS) and ornithine d-aminotransferase (OAT) and the down-regulation of proline dehydrogenase (PDH) were induced by SNP treatment, thereby accelating proline production. Additionally, SNP treatment elevated protein expression and activity of alternative oxidase (AOX). The above effects induced upon SNP were partly weakened by neomycin. Therefore, IP3 mediated NO-activated GABA and proline accumulation as well as AOX, thus inducing chilling tolerance in postharvest peach fruit.


Assuntos
Frutas/química , Inositol 1,4,5-Trifosfato/metabolismo , Óxido Nítrico/metabolismo , Prunus persica/metabolismo , Aldeído Desidrogenase/metabolismo , Temperatura Baixa , Armazenamento de Alimentos , Frutas/metabolismo , Glutamato Descarboxilase/metabolismo , Proteínas Mitocondriais/metabolismo , Oxirredutases/metabolismo , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/metabolismo , Proteínas de Plantas/metabolismo , Prolina/metabolismo , Prunus persica/química , Prunus persica/enzimologia , Ácido gama-Aminobutírico/metabolismo
8.
Life Sci ; 229: 277-287, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31150687

RESUMO

AIMS: Secreted protein acidic and rich in cysteine, (SPARC), is a matricellular protein implicated in the modulation of the extracellular matrix (ECM) and mitochondrial proteins expression. MAIN METHODS: To study the mechanism through which SPARC is involved in the possible link between ECM and mitochondria, C2C12 myoblasts were cultured with/without the exogenous addition/inhibition of SPARC as well as activation/inhibition of adenosine monophosphate-activated protein kinase (AMPK). Electrical pulse stimulation (EPS), was applied for 2 days in myotubes. KEY FINDINGS: The expressions of ECM-related (integrin-linked kinase (ILK), glycogen synthase kinase-3 beta (GSK-3ß), phosphorylated-GSK-3ß (p-GSK-3ß) and collagen 1a1), mitochondrial-related (AMPK, phosphorylated-AMPK (p-AMPK), succinate dehydrogenase (SDHB) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (Pgc1α)) and SPARC proteins and/or genes were measured after modulation of SPARC and/or AMPK as well as with or without EPS. The addition of SPARC in C2C12 myoblast increased the expression of ILK, p-GSK-3ß and p-AMPK whereas anti-SPARC antibody decreased them at different incubation times (0, 10, and 30 min, and 6 h). The AMPK activation increased SPARC, collagen 1a1, p-AMPK and SDHB proteins level, however, AMPK inhibition blunted the effects. EPS induced Sparc and Pgc1a genes expression. SIGNIFICANCE: Sparc, an EPS-induced gene, may be involved in the link between ECM remodeling and mitochondrial function in muscle via its interaction with ILK/AMPK.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Matriz Extracelular/metabolismo , Mitocôndrias/metabolismo , Proteínas Mitocondriais/metabolismo , Mioblastos/metabolismo , Osteonectina/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Quinases Ativadas por AMP/genética , Animais , Células Cultivadas , Estimulação Elétrica , Regulação da Expressão Gênica , Camundongos , Mitocôndrias/genética , Proteínas Mitocondriais/genética , Mioblastos/citologia , Osteonectina/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Fosforilação , Proteínas Serina-Treonina Quinases/genética
9.
J Biol Regul Homeost Agents ; 33(3): 753-761, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31198013

RESUMO

The root cause of obstructive sleep apnea-hypopnea syndrome (OSAHS) is repeated hypoxia during sleep. The genioglossus is one of the most important upper airway dilatation muscles and is important for maintaining normal oxygen supply during sleep. Hypoxia can directly affect the energy metabolism level of the genioglossus muscle, thereby weakening muscle function. MicroRNAs (miRNAs) can regulate mitochondrial function at the post-transcriptional level and achieve recovery or even enhancement of genioglossus function, but the specific mechanism is still unclear. In this study, an intermittent hypoxic cell model was established to detect the effects of hypoxia on the proliferation and apoptosis of Genioglossus muscle satellite cells (GG MuSCs), and the damage to the mitochondrial structure and function was assessed by transmission electron microscopy and mitochondrial membrane potential. Then, miR-17-5p was upregulated and downregulated by miRNA mimics and inhibitors, respectively, and bioinformatics analysis was used to predict and validate the target genes of miR-17-5p. The results showed that the hypoxic environment affected the proliferation of GG MuSCs and mitochondrial membrane potential, which promoted the occurrence of apoptosis and mitochondrial edema. After upregulation of miR-17-5p, cell proliferative capacity and mitochondrial function were restored. Bioinformatics prediction and gene and protein level analyses found that Mfn2 may be a target gene of miR-17-5p. .


Assuntos
GTP Fosfo-Hidrolases/metabolismo , MicroRNAs/genética , Mitocôndrias , Proteínas Mitocondriais/metabolismo , Células Satélites de Músculo Esquelético/citologia , Apoptose , Hipóxia Celular , Proliferação de Células , Humanos , Potencial da Membrana Mitocondrial
10.
Vet Microbiol ; 234: 51-60, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31213272

RESUMO

E5 protein, the major oncoprotein of the bovine Deltapapillomavirus genus, has been detected in 17 of the 19 urothelial cancers by molecular and morphological procedures. In 10 urothelial cancers, the oxygen sensitive subunit HIF-1α, which is upregulated by hypoxia, was overexpressed. Mitophagy, the selective autophagic removal of dysfunctional mitochondria, was upregulated in hypoxic neoplastic cells infected by BPVs which was mediated by FUNDC1, a mitochondrial outer-membrane protein. The FUNDC1 receptor was amplified by PCR, and amplicon sequencing showed a 100% homology with bovine FUNDC1 sequences deposited in GenBank (accession number: NM_001104982). Both transcripts and protein levels of FUNDC1 were significantly decreased in hypoxic neoplastic cells relative to healthy, non-neoplastic cells. FUNDC1 interacted with the LC3 protein, a marker of autophagosome (mitophagosome) membrane, the Hsc70/Hsp70 chaperone, and Bag3 co-chaperone. Bag3 may play a role in mitophagosome formation together with the Synpo2 protein, and may be involved in the degradation of Hsc70/Hsp70-bound CHIP-ubiquitinated cargoes, in association with its chaperone. Ultrastructural findings revealed the presence of mitochondria exhibiting severe fragmentation and loss of cristae, as well as numerous mitochondria-containing autophagosomes. Total and phosphorylated GTPase dynamin-related protein 1 (DRP1), which plays a crucial role in mitochondrial fission, a pre-requisite for mitophagy, was overexpressed at the mitochondrial level. Total and phosphorylated mitochondrial fission factor (Mff), mitochondrial fission protein 1 (Fis1), mitochondrial dynamics 51 (MiD51), and MiD49, which are DRP1 receptors responsible and/or co-responsible for its mitochondrial recruitment were overexpressed.


Assuntos
Deltapapillomavirus/patogenicidade , Mitocôndrias/patologia , Degradação Mitocondrial , Proteínas Mitocondriais/metabolismo , Urotélio/virologia , Animais , Bovinos , Feminino , Proteínas de Ligação ao GTP/genética , Hipóxia , Microscopia Eletrônica de Transmissão , Mitocôndrias/ultraestrutura , Mitocôndrias/virologia , Proteínas Mitocondriais/genética , Proteínas Oncogênicas Virais/genética , Fosforilação , Urotélio/citologia , Urotélio/patologia
11.
Plant Physiol Biochem ; 141: 415-422, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31229926

RESUMO

This study aimed to investigate the possible alleviating effect of chitosan on salt-induced growth retardation and oxidative stress and to elucidate whether this effect is linked to activation of mitochondrial respiration on the basis of alternative respiration in maize seedlings. Salt stress significantly reduced root length and plant height in comparison to the control, whereas foliar application of chitosan ameliorated the adverse effect of salinity to a certain degree. Moreover, chitosan resulted in plant growth promotion as compared to unstressed seedlings. The separate applications of chitosan and salt had a stimulatory effect on the activities of antioxidant enzymes; however, combined application of chitosan and salt were more effective than that of chitosan or salt alone. Similarly, mitochondrial total respiration rate (Vt) and alternative respiration capacity (Valt) were increased by separate applications of chitosan and salt; however, the combination of chitosan and salt gave the highest values for these parameters. The highest values of Valt/Vt was recorded at seedlings treated with salt plus chitosan. Similarly, cytochrome respiration capacity was also increased by chitosan in both stress-free and stressed conditions. In addition, AOX1, encoding alternative oxidase, was significantly upregulated by chitosan and/or salt. The maximum transcript level was recorded at seedlings treated with salt plus chitosan. Chitosan also significantly decreased superoxide anion and hydrogen peroxide contents and lipid peroxidation level under normal and the stressed conditions. These results suggest that the mitigating effect of chitosan on salt stress is linked to activation of alternative respiration at biochemical and molecular level.


Assuntos
Quitosana/química , Regulação da Expressão Gênica de Plantas , Proteínas Mitocondriais/metabolismo , Oxirredutases/metabolismo , Proteínas de Plantas/metabolismo , Tolerância ao Sal , Plântula/genética , Zea mays/genética , Antioxidantes/metabolismo , Citocromos/metabolismo , Perfilação da Expressão Gênica , Peroxidação de Lipídeos , Mitocôndrias/metabolismo , Proteínas Mitocondriais/genética , Estresse Oxidativo , Oxirredutases/genética , Proteínas de Plantas/genética , RNA/metabolismo , Estresse Fisiológico , Zea mays/enzimologia
12.
Biochemistry (Mosc) ; 84(Suppl 1): S225-S232, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31213204

RESUMO

Mitochondria play a crucial role in energy production, general cell metabolism, cell signaling, and apoptosis. Mitochondria are also the main source of reactive oxygen species, especially in the case of their dysfunction. Therefore, damaged or even superfluous mitochondria not required for normal cell functioning represent risk factors and should be removed in order to maintain cell homeostasis. Mitochondria removal occurs via mitophagy, a type of selective autophagy (from Greek autos, self and phagein, to eat) that takes place in parallel with mitochondrial biogenesis and other processes. This review outlines general views on autophagy and mitophagy and summarizes information on the autophagy-related (Atg) proteins and their complexes involved in these processes. Yeast, especially Saccharomyces cerevisiae, is a convenient model system for studying molecular mechanisms of mitophagy because yeast genome, transcriptome, and proteome have been well characterized and because genetic manipulations with yeast are relatively simple and fast. Furthermore, yeast contain a number of orthologs of human proteins. Mitophagy in yeast is promoted by various factors, such as starvation, aging, oxidative stress, mitochondrial dysfunction, signaling proteins, and modification of mitochondrial proteins. In this review, we discuss molecular mechanisms underlying mitophagy and its regulation in yeast and present examples of relationships between mitophagy and ubiquitination-deubiquitination processes, as well as between mitophagy and other types of autophagy.


Assuntos
Proteínas Relacionadas à Autofagia/metabolismo , Autofagia , Mitocôndrias/metabolismo , Degradação Mitocondrial , Proteínas Mitocondriais/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Homeostase , Ubiquitinação
13.
Microb Cell Fact ; 18(1): 88, 2019 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-31122246

RESUMO

BACKGROUND: There have been many successful strategies to implement xylose metabolism in Saccharomyces cerevisiae, but no effort has so far enabled xylose utilization at rates comparable to that of glucose (the preferred sugar of this yeast). Many studies have pointed towards the engineered yeast not sensing that xylose is a fermentable carbon source despite growing and fermenting on it, which is paradoxical. We have previously used fluorescent biosensor strains to in vivo monitor the sugar signalome in yeast engineered with xylose reductase and xylitol dehydrogenase (XR/XDH) and have established that S. cerevisiae senses high concentrations of xylose with the same signal as low concentration of glucose, which may explain the poor utilization. RESULTS: In the present study, we evaluated the effects of three deletions (ira2∆, isu1∆ and hog1∆) that have recently been shown to display epistatic effects on a xylose isomerase (XI) strain. Through aerobic and anaerobic characterization, we showed that the proposed effects in XI strains were for the most part also applicable in the XR/XDH background. The ira2∆isu1∆ double deletion led to strains with the highest specific xylose consumption- and ethanol production rates but also the lowest biomass titre. The signalling response revealed that ira2∆isu1∆ changed the low glucose-signal in the background strain to a simultaneous signalling of high and low glucose, suggesting that engineering of the signalome can improve xylose utilization. CONCLUSIONS: The study was able to correlate the previously proposed beneficial effects of ira2∆, isu1∆ and hog1∆ on S. cerevisiae xylose uptake, with a change in the sugar signalome. This is in line with our previous hypothesis that the key to resolve the xylose paradox lies in the sugar sensing and signalling networks. These results indicate that the future engineering targets for improved xylose utilization should probably be sought not in the metabolic networks, but in the signalling ones.


Assuntos
Glucose , Redes e Vias Metabólicas/genética , Saccharomyces cerevisiae , Xilose , Transporte Biológico , Fermentação , Deleção de Genes , Glucose/genética , Glucose/metabolismo , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Plasmídeos , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/crescimento & desenvolvimento , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Transdução de Sinais , Xilose/genética , Xilose/metabolismo
14.
Plant Cell Physiol ; 60(8): 1734-1746, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31076755

RESUMO

Pentatricopeptide repeat (PPR) proteins play crucial roles in intron splicing, which is important for RNA maturation. Identification of novel PPR protein with the function of intron splicing would help to understand the RNA splicing mechanism. In this study, we identified the maize empty pericarp602 (emp602) mutants, the mature kernels of which showed empty pericarp phenotype. We cloned the Emp602 gene from emp602 mutants and revealed that Emp602 encodes a mitochondrial-localized P-type PPR protein. We further revealed that Emp602 is specific for the cis-splicing of mitochondrial Nad4 intron 1 and intron 3, and mutation of Emp602 led to the loss of mature Nad4 transcripts. The loss of function of Emp602 nearly damaged the assembly and accumulation of complex I and arrested mitochondria formation, which arrested the seed development. The failed assembly of complex I triggers significant upregulation of Aox expression in emp602 mutants. Transcriptome analysis showed that the expression of mitochondrial-related genes, e.g. the genes associated with mitochondrial inner membrane presequence translocase complex and electron carrier activity, were extensively upregulated in emp602 mutant. These results demonstrate that EMP602 functions in the splicing of Nad4 intron 1 and intron 3, and the loss of function of Emp602 arrested maize seed development by disrupting the mitochondria complex I assembly.


Assuntos
Sementes/metabolismo , Zea mays/metabolismo , Regulação da Expressão Gênica de Plantas/genética , Regulação da Expressão Gênica de Plantas/fisiologia , Íntrons/genética , Íntrons/fisiologia , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/crescimento & desenvolvimento , Plantas Geneticamente Modificadas/metabolismo , Processamento de RNA/genética , Processamento de RNA/fisiologia , Sementes/genética , Sementes/crescimento & desenvolvimento , Zea mays/genética , Zea mays/crescimento & desenvolvimento
15.
Plant Cell Physiol ; 60(8): 1829-1841, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31119292

RESUMO

Alternative oxidase (AOX) has been reported to be involved in mitochondrial function and redox homeostasis, thus playing an essential role in plant growth as well as stress responses. However, its biological functions in nonseed plants have not been well characterized. Here, we report that AOX participates in plant salt tolerance regulation in moss Physcomitrella patens (P. patens). AOX is highly conserved and localizes to mitochondria in P. patens. We observed that PpAOX rescued the impaired cyanide (CN)-resistant alternative (Alt) respiratory pathway in Arabidopsis thaliana (Arabidopsis) aox1a mutant. PpAOX transcription and Alt respiration were induced upon salt stress in P. patens. Using homologous recombination, we generated PpAOX-overexpressing lines (PpAOX OX). PpAOX OX plants exhibited higher Alt respiration and lower total reactive oxygen species accumulation under salt stress condition. Strikingly, we observed that PpAOX OX plants displayed decreased salt tolerance. Overexpression of PpAOX disturbed redox homeostasis in chloroplasts. Meanwhile, chloroplast structure was adversely affected in PpAOX OX plants in contrast to wild-type (WT) P. patens. We found that photosynthetic activity in PpAOX OX plants was also lower compared with that in WT. Together, our work revealed that AOX participates in plant salt tolerance in P. patens and there is a functional link between mitochondria and chloroplast under challenging conditions.


Assuntos
Bryopsida/metabolismo , Cloroplastos/metabolismo , Proteínas Mitocondriais/metabolismo , Oxirredutases/metabolismo , Proteínas de Plantas/metabolismo , Plantas Tolerantes a Sal/metabolismo , Bryopsida/genética , Regulação da Expressão Gênica de Plantas/genética , Regulação da Expressão Gênica de Plantas/fisiologia , Proteínas Mitocondriais/genética , Oxirredução , Oxirredutases/genética , Proteínas de Plantas/genética , Plantas Tolerantes a Sal/genética
16.
Artif Cells Nanomed Biotechnol ; 47(1): 1653-1661, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31043087

RESUMO

Finding novel therapeutic agent for the treatment of cerebral ischemia is urgently required. These experiments explored the potential roles of 6-Gingerols (6G) in hypoxia-stimulated rat PC-12 cells. Cell viability, apoptosis and its related proteins were studied by the approaches of MTT assay, flow cytometry assay and Western blot analysis, respectively. In addition, whether 6G achieved its functions in hypoxia-induced injury through miR-103 was illustrated. Moreover, the associated signalling pathways were investigated. Obviously, hypoxia treatment blocked cell viability and enhanced apoptosis while this trend was ameliorated by 6G. Then we observed that hypoxia administration up-regulated miR-103 expression and 6G could further increase miR-103 expression in hypoxia-stimulated PC-12 cells. Inhibition of miR-103 attenuated the neuroprotective effects of 6G on hypoxia-treated PC-12 cells. Moreover, Bcl2/adenovirus EIB 19kD-interacting protein 3 (BNIP3) was a target of miR-103 and BNIP3 upregulation also attenuated the neuroprotective impact of 6G on hypoxia-treated PC-12 cells. Hypoxia activated the p38MAPK and JNK pathways were inactivated by 6G. To sum up, 6G protected hypoxia-stimulated PC-12 cells through miR-103-mediatated down-regulation of BNIP3 by inhibiting p38 MAPK and JNK pathways. Highlights 6-Gingerols (6G) is a promising agent for cerebral ischemia therapy. The neuroprotective effects of 6G are mediated by miR-103 and BNIP3. Up-regulation of miR-103 exerts neuroprotective effects.


Assuntos
Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Catecóis/farmacologia , Álcoois Graxos/farmacologia , Proteínas de Membrana/metabolismo , MicroRNAs/genética , Proteínas Mitocondriais/metabolismo , Animais , Hipóxia Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Citoproteção/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Proteínas de Membrana/genética , Proteínas Mitocondriais/genética , Células PC12 , Ratos , Regulação para Cima/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
17.
Mediators Inflamm ; 2019: 4050796, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31065234

RESUMO

Mitochondrial dysfunction has been established as a common feature of neurodegenerative disorders that contributes to disease pathology by causing impaired cellular energy production. Mitochondrial molecules released into the extracellular space following neuronal damage or death may also play a role in these diseases by acting as signaling molecules called damage-associated molecular patterns (DAMPs). Mitochondrial DAMPs have been shown to initiate proinflammatory immune responses from nonneuronal glial cells, including microglia and astrocytes; thereby, they have the potential to contribute to the chronic neuroinflammation present in these disorders accelerating the degeneration of neurons. In this review, we highlight the mitochondrial DAMPs cytochrome c (CytC), mitochondrial transcription factor A (TFAM), and cardiolipin and explore their potential role in the central nervous system disorders including Alzheimer's disease and Parkinson's disease, which are characterized by neurodegeneration and chronic neuroinflammation.


Assuntos
Inflamação/imunologia , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Doenças Neurodegenerativas/imunologia , Animais , Citocromos c/metabolismo , Proteínas de Ligação a DNA/metabolismo , Humanos , Inflamação/metabolismo , Proteínas Mitocondriais/metabolismo , Doenças Neurodegenerativas/metabolismo , Fatores de Transcrição/metabolismo
18.
Mol Med Rep ; 19(6): 4973-4979, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31059091

RESUMO

Atherosclerosis is a chronic and progressive disease. Its morbidity and mortality rates have demonstrated an increase in recent years. The present study aimed to explore the role of sirtuin (SIRT) 4 in the development of atherosclerosis. Alterations in SIRT4 expression in response to oxidized low density lipoprotein (oxLDL) were quantified in human umbilical vein endothelial cells (HUVECs) using western blotting. Cell counting kit­8 and flow cytometry assays were used in order to explore the effects of SIRT4 on HUVEC proliferation and apoptosis. The effect of SIRT4 on the expression of inflammatory factors in HUVECs was analyzed using ELISA. The expression and phosphorylation of proteins in the phosphoinositide 3­kinase (PI3K)/protein kinase B (Akt)/nuclear factor (NF)­κB pathway were comparatively analyzed using western blotting. Nuclear translocation of p65 NF­κB was examined using immunofluorescence. The present study indicated that oxLDL treatment decreased the expression of SIRT4 in HUVECs in a dose­ and time­dependent manner. SIRT4 overexpression promoted oxLDL­induced HUVEC proliferation and inhibited cell apoptosis. Furthermore, SIRT4 overexpression suppressed the PI3K/Akt/NF­κB pathway by inhibiting PI3K phosphorylation and phosphorylated (p)­Akt, p­nuclear factor of kappa light polypeptide gene enhancer in B­cells inhibitor α and p­p65 NF­κB expression; blocking p65 NF­κB nuclear translocation and decreasing interleukin (IL)­1ß, IL­6, and tumor necrosis factor α expression in oxLDL­induced HUVECs. In conclusion, SIRT4 overexpression enhanced HUVEC survival, suppressed the PI3K/Akt/NF­κB signaling pathway and inhibited the expression of inflammatory cytokines in oxLDL­induced HUVECs.


Assuntos
Lipoproteínas LDL/toxicidade , Proteínas Mitocondriais/metabolismo , Transdução de Sinais/efeitos dos fármacos , Sirtuínas/metabolismo , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana , Humanos , Interleucina-1beta/metabolismo , Proteínas Mitocondriais/genética , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Sirtuínas/genética , Fator de Transcrição RelA/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
19.
Plant Cell Rep ; 38(8): 981-990, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31065779

RESUMO

KEY MESSAGE: The ISC Fe-S cluster biosynthetic pathway would play a key role in the regulation of iron and sulfur homeostasis in plants. The Arabidopsis thaliana mitochondrial cysteine desulfurase AtNFS1 has an essential role in cellular ISC Fe-S cluster assembly, and this pathway is one of the main sinks for iron (Fe) and sulfur (S) in the plant. In different plant species it has been reported a close relationship between Fe and S metabolisms; however, the regulation of both nutrient homeostasis is not fully understood. In this study, we have characterized AtNFS1 overexpressing and knockdown mutant Arabidopsis plants. Plants showed alterations in the ISC Fe-S biosynthetic pathway genes and in the activity of Fe-S enzymes. Genes involved in Fe and S uptakes, assimilation, and regulation were up-regulated in overexpressing plants and down-regulated in knockdown plants. Furthermore, the plant nutritional status in different tissues was in accordance with those gene activities: overexpressing lines accumulated increased amounts of Fe and S and mutant plant had lower contents of S. In summary, our results suggest that the ISC Fe-S cluster biosynthetic pathway plays a crucial role in the homeostasis of Fe and S in plants, and that it may be important in their regulation.


Assuntos
Ferro/metabolismo , Mitocôndrias/metabolismo , Proteínas Mitocondriais/metabolismo , Enxofre/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Liases de Carbono-Enxofre/genética , Liases de Carbono-Enxofre/metabolismo , Proteínas com Ferro-Enxofre/genética , Proteínas com Ferro-Enxofre/metabolismo , Mitocôndrias/genética , Proteínas Mitocondriais/genética
20.
Neurochem Res ; 44(7): 1773-1779, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31102025

RESUMO

Spinal muscular atrophy (SMA) is an inherited disease characterized by progressive motor neuron death and subsequent muscle weakness and is caused by deletion or mutation of survival motor neuron (SMN) 1 gene. Protecting spinal motor neuron is an effective clinical strategy for SMA. The purpose of this study was to investigate the potential effect of an anti-epileptic drug levetiracetam on SMA. In the present study, we used differentiated spinal motor neurons (MNs) from SMA patient-derived induced pluripotent stem cells (SMA-iPSCs) to investigate the effect of levetiracetam. Levetiracetam promoted neurite elongation in SMA-iPSCs-MNs. TUNEL-positive spinal motor neurons were significantly reduced by levetiracetam in SMA-iPSCs-MNs. In addition, the expression level of cleaved-caspase 3 was decreased by levetiracetam in SMA-iPSCs-MNs. Furthermore, levetiracetam improved impaired mitochondrial function in SMA-iPSCs-MNs. On the other hand, levetiracetam did not affect the expression level of SMN protein in SMA-iPSCs-MNs. These findings indicate that levetiracetam has a neuroprotective effect for SMA.


Assuntos
Células-Tronco Pluripotentes Induzidas/efeitos dos fármacos , Levetiracetam/uso terapêutico , Neurônios Motores/efeitos dos fármacos , Atrofia Muscular Espinal/prevenção & controle , Neuritos/efeitos dos fármacos , Fármacos Neuroprotetores/uso terapêutico , Apoptose/efeitos dos fármacos , Chaperonina 60/metabolismo , Humanos , Células-Tronco Pluripotentes Induzidas/patologia , Mitocôndrias/efeitos dos fármacos , Proteínas Mitocondriais/metabolismo , Neurônios Motores/patologia , Atrofia Muscular Espinal/patologia , Neuritos/patologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA