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1.
Biomed Pharmacother ; 142: 112041, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34411916

RESUMO

Senescence is a crucial player in several metabolic disorders and chronic inflammatory diseases. Recent data prove the involvement of hepatocyte senescence in the development of NAFLD (non-alcoholic fatty liver disease). As the main energy and ROS (reactive oxygen species) producing organelle, mitochondria play the central role in accelerated senescence and diseases development. In this review, we focus on the role of regulation of mitochondrial Ca2+ homeostasis, NAD+/NADH ratio, UPRmt (mitochondrial unfolded protein response), phospholipids and fatty acid oxidation in hepatic senescence, lifespan and NAFLD disease susceptibility. Additionally, the involvement of mitochondrial and nuclear mutations in lifespan-modulation and NAFLD development is discussed. While nuclear and mitochondria DNA mutations and SNPs (single nucleotide polymorphisms) can be used as effective diagnostic markers and targets for treatments, advanced age should be considered as an independent risk factor for NAFLD development.

2.
Int J Mol Sci ; 22(16)2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34445477

RESUMO

Mitochondria-derived peptides (MDPs) are small peptides hidden in the mitochondrial DNA, maintaining mitochondrial function and protecting cells under different stresses. Currently, three types of MDPs have been identified: Humanin, MOTS-c and SHLP1-6. MDPs have demonstrated anti-apoptotic and anti-inflammatory activities, reactive oxygen species and oxidative stress-protecting properties both in vitro and in vivo. Recent research suggests that MDPs have a significant cardioprotective role, affecting CVDs (cardiovascular diseases) development and progression. CVDs are the leading cause of death globally; this term combines disorders of the blood vessels and heart. In this review, we focus on the recent progress in understanding the relationships between MDPs and the main cardiovascular risk factors (atherosclerosis, insulin resistance, hyperlipidaemia and ageing). We also will discuss the therapeutic application of MDPs, modified and synthetic MDPs, and their potential as novel biomarkers and therapeutic targets.


Assuntos
Doenças Cardiovasculares/tratamento farmacológico , Mitocôndrias/metabolismo , Proteínas Mitocondriais/metabolismo , Fragmentos de Peptídeos/farmacologia , Animais , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/patologia , Humanos
3.
Int J Mol Sci ; 22(13)2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34203309

RESUMO

The prevalence of NAFLD (non-alcoholic fatty liver disease) is a rapidly increasing problem, affecting a huge population around the globe. However, CVDs (cardiovascular diseases) are the most common cause of mortality in NAFLD patients. Atherogenic dyslipidemia, characterized by plasma hypertriglyceridemia, increased small dense LDL (low-density lipoprotein) particles, and decreased HDL-C (high-density lipoprotein cholesterol) levels, is often observed in NAFLD patients. In this review, we summarize recent genetic evidence, proving the diverse nature of metabolic pathways involved in NAFLD pathogenesis. Analysis of available genetic data suggests that the altered operation of fatty-acid ß-oxidation in liver mitochondria is the key process, connecting NAFLD-mediated dyslipidemia and elevated CVD risk. In addition, we discuss several NAFLD-associated genes with documented anti-atherosclerotic or cardioprotective effects, and current pharmaceutical strategies focused on both NAFLD treatment and reduction of CVD risk.


Assuntos
Aterosclerose/metabolismo , Doenças Cardiovasculares/metabolismo , Dislipidemias/metabolismo , Fígado/metabolismo , Animais , Humanos , Metabolismo dos Lipídeos/genética , Metabolismo dos Lipídeos/fisiologia
4.
Int J Mol Sci ; 22(13)2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34201756

RESUMO

Diabetes mellitus and related disorders significantly contribute to morbidity and mortality worldwide. Despite the advances in the current therapeutic methods, further development of anti-diabetic therapies is necessary. Mitochondrial dysfunction is known to be implicated in diabetes development. Moreover, specific types of mitochondrial diabetes have been discovered, such as MIDD (maternally inherited diabetes and deafness) and DAD (diabetes and Deafness). Hereditary mitochondrial disorders are caused by certain mutations in the mitochondrial DNA (mtDNA), which encodes for a substantial part of mitochondrial proteins and mitochondrial tRNA necessary for mitochondrial protein synthesis. Study of mtDNA mutations is challenging because the pathogenic phenotype associated with such mutations depends on the level of its heteroplasmy (proportion of mtDNA copies carrying the mutation) and can be tissue-specific. Nevertheless, modern sequencing methods have allowed describing and characterizing a number of mtDNA mutations associated with human disorders, and the list is constantly growing. In this review, we provide a list of mtDNA mutations associated with diabetes and related disorders and discuss the mechanisms of their involvement in the pathology development.


Assuntos
Diabetes Mellitus/genética , Genoma Mitocondrial/genética , Inflamação/genética , Mutação , Animais , Doença Crônica , DNA Mitocondrial/genética , Surdez/genética , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/fisiopatologia , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Tipo 2/genética , Feminino , Humanos , Camundongos , Doenças Mitocondriais/genética
5.
Int J Mol Sci ; 22(9)2021 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-33923295

RESUMO

NAFLD (non-alcoholic fatty liver disease) is a widespread liver disease that is often linked with other life-threatening ailments (metabolic syndrome, insulin resistance, diabetes, cardiovascular disease, atherosclerosis, obesity, and others) and canprogress to more severe forms, such as NASH (non-alcoholic steatohepatitis), cirrhosis, and HCC (hepatocellular carcinoma). In this review, we summarized and analyzed data about single nucleotide polymorphism sites, identified in genes related to NAFLD development and progression. Additionally, the causative role of mitochondrial mutations and mitophagy malfunctions in NAFLD is discussed. The role of mitochondria-related metabolites of the urea cycle as a new non-invasive NAFLD biomarker is discussed. While mitochondria DNA mutations and SNPs (single nucleotide polymorphisms) canbe used as effective diagnostic markers and target for treatments, age and ethnic specificity should be taken into account.


Assuntos
DNA Mitocondrial/genética , Mitocôndrias/genética , Mutação , Hepatopatia Gordurosa não Alcoólica/patologia , Polimorfismo de Nucleotídeo Único , Animais , Progressão da Doença , Humanos , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Fatores de Risco
6.
Int J Mol Sci ; 22(8)2021 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-33920227

RESUMO

Polycystic ovarian syndrome (PCOS) is the most common endocrine-metabolic disorder affecting a vast population worldwide; it is linked with anovulation, mitochondrial dysfunctions and hormonal disbalance. Mutations in mtDNA have been identified in PCOS patients and likely play an important role in PCOS aetiology and pathogenesis; however, their causative role in PCOS development requires further investigation. As a low-grade chronic inflammation disease, PCOS patients have permanently elevated levels of inflammatory markers (TNF-α, CRP, IL-6, IL-8, IL-18). In this review, we summarise recent data regarding the role of mtDNA mutations and mitochondrial malfunctions in PCOS pathogenesis. Furthermore, we discuss recent papers dedicated to the identification of novel biomarkers for early PCOS diagnosis. Finally, traditional and new mitochondria-targeted treatments are discussed. This review intends to emphasise the key role of oxidative stress and chronic inflammation in PCOS pathogenesis; however, the exact molecular mechanism is mostly unknown and requires further investigation.


Assuntos
DNA Mitocondrial/genética , Inflamação/genética , Mitocôndrias/genética , Síndrome do Ovário Policístico/genética , Feminino , Humanos , Inflamação/diagnóstico , Inflamação/patologia , Mitocôndrias/patologia , Mutação/genética , Estresse Oxidativo/genética , Síndrome do Ovário Policístico/diagnóstico , Síndrome do Ovário Policístico/patologia
7.
J Genet Eng Biotechnol ; 18(1): 60, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33025290

RESUMO

BACKGROUND: Nitroreductases are a family of evolutionarily related proteins catalyzing the reduction of nitro-substituted compounds. Nitroreductases are widespread enzymes, but nearly all modern research and practical application have been concentrated on the bacterial proteins, mainly nitroreductases of Escherichia coli. The main aim of this study is to describe the phylogenic distribution of the nitroreductases in the photosynthetic eukaryotes (Viridiplantae) to highlight their structural similarity and areas for future research and application. RESULTS: This study suggests that homologs of nitroreductase proteins are widely presented also in Viridiplantae. Maximum likelihood phylogenetic tree reconstruction method and comparison of the structural models suggest close evolutional relation between cyanobacterial and Viridiplantae nitroreductases. CONCLUSIONS: This study provides the first attempt to understand the evolution of nitroreductase protein family in Viridiplantae. Our phylogeny estimation and preservation of the chloroplasts/mitochondrial localization indicate the evolutional origin of the plant nitroreductases from the cyanobacterial endosymbiont. A defined high level of the similarity on the structural level suggests conservancy also for the functions. Directions for the future research and industrial application of the Viridiplantae nitroreductases are discussed.

8.
Front Plant Sci ; 11: 573564, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33123183

RESUMO

The processes of plant nutrition, stress tolerance, plant growth, and development are strongly dependent on transport of mineral nutrients across cellular membranes. Plant membrane transporters are key components of these processes. Among various membrane transport proteins, the monovalent cation proton antiporter (CPA) superfamily mediates a broad range of physiological and developmental processes such as ion and pH homeostasis, development of reproductive organs, chloroplast operation, and plant adaptation to drought and salt stresses. CPA family includes plasma membrane-bound Na+/H+ exchanger (NhaP) and intracellular Na+/H+ exchanger NHE (NHX), K+ efflux antiporter (KEA), and cation/H+ exchanger (CHX) family proteins. In this review, we have completed the phylogenetic inventory of CPA transporters and undertaken a comprehensive evolutionary analysis of their development. Compared with previous studies, we have significantly extended the range of plant species, including green and red algae and Acrogymnospermae into phylogenetic analysis. Our data suggest that the multiplication and complexation of CPA isoforms during evolution is related to land colonisation by higher plants and associated with an increase of different tissue types and development of reproductive organs. The new data extended the number of clades for all groups of CPAs, including those for NhaP/SOS, NHE/NHX, KEA, and CHX. We also critically evaluate the latest findings on the biological role, physiological functions and regulation of CPA transporters in relation to their structure and phylogenetic position. In addition, the role of CPA members in plant tolerance to various abiotic stresses is summarized, and the future priority directions for CPA studies in plants are discussed.

9.
Curr Microbiol ; 77(4): 517-521, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31728698

RESUMO

For several decades, dirigent (DIR) domain-containing proteins have been assumed to be green lineage-specific, responsible for the defence response and lignan/lignin biosynthesis. Despite their high potential in terms of biotechnology and chemistry, to date there have been very few well-studied plant DIRs. However, recent achievements in sequencing technologies have allowed for discovery of DIR genes in bacteria. This prospective study suggests expansion of the focus of research to consider the existence of bacterial DIRs. It also considers the outlook for understanding DIR functioning with respect to the fields of green lineage evolution, organic synthesis, and biotechnology.


Assuntos
Bactérias/genética , Proteínas de Bactérias/genética , Bactérias/metabolismo , Lignanas/biossíntese , Lignina/biossíntese , Família Multigênica , Filogenia , Proteínas de Plantas/genética , Estudos Prospectivos , Domínios Proteicos
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