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1.
Proc Natl Acad Sci U S A ; 121(28): e2315043121, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38968128

RESUMO

Only 30% of embryos from in vitro fertilized oocytes successfully implant and develop to term, leading to repeated transfer cycles. To reduce time-to-pregnancy and stress for patients, there is a need for a diagnostic tool to better select embryos and oocytes based on their physiology. The current standard employs brightfield imaging, which provides limited physiological information. Here, we introduce METAPHOR: Metabolic Evaluation through Phasor-based Hyperspectral Imaging and Organelle Recognition. This non-invasive, label-free imaging method combines two-photon illumination and AI to deliver the metabolic profile of embryos and oocytes based on intrinsic autofluorescence signals. We used it to classify i) mouse blastocysts cultured under standard conditions or with depletion of selected metabolites (glucose, pyruvate, lactate); and ii) oocytes from young and old mouse females, or in vitro-aged oocytes. The imaging process was safe for blastocysts and oocytes. The METAPHOR classification of control vs. metabolites-depleted embryos reached an area under the ROC curve (AUC) of 93.7%, compared to 51% achieved for human grading using brightfield imaging. The binary classification of young vs. old/in vitro-aged oocytes and their blastulation prediction using METAPHOR reached an AUC of 96.2% and 82.2%, respectively. Finally, organelle recognition and segmentation based on the flavin adenine dinucleotide signal revealed that quantification of mitochondria size and distribution can be used as a biomarker to classify oocytes and embryos. The performance and safety of the method highlight the accuracy of noninvasive metabolic imaging as a complementary approach to evaluate oocytes and embryos based on their physiology.


Assuntos
Blastocisto , Oócitos , Animais , Blastocisto/metabolismo , Camundongos , Oócitos/metabolismo , Feminino , Organelas/metabolismo , Imagem Óptica/métodos
2.
Commun Biol ; 7(1): 832, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38977899

RESUMO

An important question in cell biology is how cytoskeletal proteins evolved and drove the development of novel structures and functions. Here we address the origin of SPIRE actin nucleators. Mammalian SPIREs work with RAB GTPases, formin (FMN)-subgroup actin assembly proteins and class-5 myosin (MYO5) motors to transport organelles along actin filaments towards the cell membrane. However, the origin and extent of functional conservation of SPIRE among species is unknown. Our sequence searches show that SPIRE exist throughout holozoans (animals and their closest single-celled relatives), but not other eukaryotes. SPIRE from unicellular holozoans (choanoflagellate), interacts with RAB, FMN and MYO5 proteins, nucleates actin filaments and complements mammalian SPIRE function in organelle transport. Meanwhile SPIRE and MYO5 proteins colocalise to organelles in Salpingoeca rosetta choanoflagellates. Based on these observations we propose that SPIRE originated in unicellular ancestors of animals providing an actin-myosin driven exocytic transport mechanism that may have contributed to the evolution of complex multicellular animals.


Assuntos
Actomiosina , Organelas , Animais , Organelas/metabolismo , Actomiosina/metabolismo , Proteínas dos Microfilamentos/metabolismo , Proteínas dos Microfilamentos/genética , Miosina Tipo V/metabolismo , Miosina Tipo V/genética , Actinas/metabolismo , Humanos , Coanoflagelados/metabolismo , Citoesqueleto de Actina/metabolismo , Evolução Biológica , Evolução Molecular , Forminas/metabolismo , Proteínas rab de Ligação ao GTP/metabolismo , Filogenia , Proteínas Nucleares
3.
Physiol Plant ; 176(4): e14418, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39004808

RESUMO

Plant organelle transcription has been studied for decades. As techniques advanced, so did the fields of mitochondrial and plastid transcriptomics. The current view is that organelle genomes are pervasively transcribed, irrespective of their size, content, structure, and taxonomic origin. However, little is known about the nature of organelle noncoding transcriptomes, including pervasively transcribed noncoding RNAs (ncRNAs). Next-generation sequencing data have uncovered small ncRNAs in the organelles of plants and other organisms, but long ncRNAs remain poorly understood. Here, we argue that publicly available third-generation long-read RNA sequencing data from plants can provide a fine-tuned picture of long ncRNAs within organelles. Indeed, given their bloated architectures, plant mitochondrial genomes are well suited for studying pervasive transcription of ncRNAs. Ultimately, we hope to showcase this new avenue of plant research while also underlining the limitations of the proposed approach.


Assuntos
RNA Antissenso , RNA Longo não Codificante , RNA de Plantas , RNA Longo não Codificante/genética , RNA Antissenso/genética , RNA de Plantas/genética , Plantas/genética , Organelas/genética , Organelas/metabolismo , RNA-Seq/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Análise de Sequência de RNA/métodos , Transcriptoma/genética
4.
Proc Natl Acad Sci U S A ; 121(30): e2319267121, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39008679

RESUMO

Migrasomes, vesicular organelles generated on the retraction fibers of migrating cells, play a crucial role in migracytosis, mediating intercellular communication. The cargoes determine the functional specificity of migrasomes. Migrasomes harbor numerous intraluminal vesicles, a pivotal component of their cargoes. The mechanism underlying the transportation of these intraluminal vesicles to the migrasomes remains enigmatic. In this study, we identified that Rab10 and Caveolin-1 (CAV1) mark the intraluminal vesicles in migrasomes. Transport of Rab10-CAV1 vesicles to migrasomes required the motor protein Myosin Va and adaptor proteins RILPL2. Notably, the phosphorylation of Rab10 by the kinase LRRK2 regulated this process. Moreover, CSF-1 can be transported to migrasomes through this mechanism, subsequently fostering monocyte-macrophage differentiation in skin wound healing, which served as a proof of the physiological importance of this transporting mechanism.


Assuntos
Caveolina 1 , Movimento Celular , Proteínas rab de Ligação ao GTP , Proteínas rab de Ligação ao GTP/metabolismo , Proteínas rab de Ligação ao GTP/genética , Humanos , Caveolina 1/metabolismo , Caveolina 1/genética , Macrófagos/metabolismo , Fosforilação , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Miosina Tipo V/metabolismo , Miosina Tipo V/genética , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/metabolismo , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/genética , Camundongos , Cadeias Pesadas de Miosina/metabolismo , Cadeias Pesadas de Miosina/genética , Transporte Biológico , Cicatrização/fisiologia , Organelas/metabolismo
5.
BMC Biol ; 22(1): 130, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38825681

RESUMO

BACKGROUND: Hydrogenosomes are a specific type of mitochondria that have adapted for life under anaerobiosis. Limited availability of oxygen has resulted in the loss of the membrane-associated respiratory chain, and consequently in the generation of minimal inner membrane potential (Δψ), and inefficient ATP synthesis via substrate-level phosphorylation. The changes in energy metabolism are directly linked with the organelle biogenesis. In mitochondria, proteins are imported across the outer membrane via the Translocase of the Outer Membrane (TOM complex), while two Translocases of the Inner Membrane, TIM22, and TIM23, facilitate import to the inner membrane and matrix. TIM23-mediated steps are entirely dependent on Δψ and ATP hydrolysis, while TIM22 requires only Δψ. The character of the hydrogenosomal inner membrane translocase and the mechanism of translocation is currently unknown. RESULTS: We report unprecedented modification of TIM in hydrogenosomes of the human parasite Trichomonas vaginalis (TvTIM). We show that the import of the presequence-containing protein into the hydrogenosomal matrix is mediated by the hybrid TIM22-TIM23 complex that includes three highly divergent core components, TvTim22, TvTim23, and TvTim17-like proteins. The hybrid character of the TvTIM is underlined by the presence of both TvTim22 and TvTim17/23, association with small Tim chaperones (Tim9-10), which in mitochondria are known to facilitate the transfer of substrates to the TIM22 complex, and the coupling with TIM23-specific ATP-dependent presequence translocase-associated motor (PAM). Interactome reconstruction based on co-immunoprecipitation (coIP) and mass spectrometry revealed that hybrid TvTIM is formed with the compositional variations of paralogs. Single-particle electron microscopy for the 132-kDa purified TvTIM revealed the presence of a single ring of small Tims complex, while mitochondrial TIM22 complex bears twin small Tims hexamer. TvTIM is currently the only TIM visualized outside of Opisthokonta, which raised the question of which form is prevailing across eukaryotes. The tight association of the hybrid TvTIM with ADP/ATP carriers (AAC) suggests that AAC may directly supply ATP for the protein import since ATP synthesis is limited in hydrogenosomes. CONCLUSIONS: The hybrid TvTIM in hydrogenosomes represents an original structural solution that evolved for protein import when Δψ is negligible and remarkable example of evolutionary adaptation to an anaerobic lifestyle.


Assuntos
Transporte Proteico , Trichomonas vaginalis , Trichomonas vaginalis/metabolismo , Proteínas de Protozoários/metabolismo , Proteínas do Complexo de Importação de Proteína Precursora Mitocondrial , Mitocôndrias/metabolismo , Organelas/metabolismo
6.
J Exp Bot ; 75(11): 3209-3213, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38845354

RESUMO

This article comments on: Casaes PA, Ferreira dos Santos JM, Silva VC, Rhem MFK, Teixeira Cota MM, de Faria SM, Rando JG, James EK, Gross E. 2024. The radiation of nodulated Chamaecrista species from the rainforest into more diverse habitats has been accompanied by a reduction in growth form and a shift from fixation threads to symbiosomes. Journal of Experimental Botany 75, 3643-3662.


Assuntos
Evolução Biológica , Organelas , Simbiose , Organelas/metabolismo
7.
Cell Rep ; 43(6): 114316, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38833370

RESUMO

Phosphate (Pi) serves countless metabolic pathways and is involved in macromolecule synthesis, energy storage, cellular signaling, and bone maintenance. Herein, we describe the coordination of Pi uptake and efflux pathways to maintain mammalian cell Pi homeostasis. We discover that XPR1, the presumed Pi efflux transporter, separately supervises rates of Pi uptake. This direct, regulatory interplay arises from XPR1 being a binding partner for the Pi uptake transporter PiT1, involving a predicted transmembrane helix/extramembrane loop in XPR1, and its hitherto unknown localization in a subset of intracellular LAMP1-positive puncta (named "XLPVs"). A pharmacological mimic of Pi homeostatic challenge is sensed by the inositol pyrophosphate IP8, which functionalizes XPR1 to respond in a temporally hierarchal manner, initially adjusting the rate of Pi efflux, followed subsequently by independent modulation of PiT1 turnover to reset the rate of Pi uptake. These observations generate a unifying model of mammalian cellular Pi homeostasis, expanding opportunities for therapeutic intervention.


Assuntos
Homeostase , Fosfatos de Inositol , Humanos , Animais , Fosfatos de Inositol/metabolismo , Receptor do Retrovírus Politrópico e Xenotrópico , Células HEK293 , Organelas/metabolismo , Transporte Biológico , Fosfatos/metabolismo , Camundongos
8.
Mol Biol Cell ; 35(8): ar107, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38922842

RESUMO

Bacterial microcompartments (BMCs) are widespread, protein-based organelles that regulate metabolism. The model for studying BMCs is the carboxysome, which facilitates carbon fixation in several autotrophic bacteria. Carboxysomes can be distinguished as type α or ß, which are structurally and phyletically distinct. We recently characterized the maintenance of carboxysome distribution (Mcd) systems responsible for spatially regulating α- and ß-carboxysomes, consisting of the proteins McdA and McdB. McdA is an ATPase that drives carboxysome positioning, and McdB is the adaptor protein that directly interacts with carboxysomes to provide cargo specificity. The molecular features of McdB proteins that specify their interactions with carboxysomes, and whether these are similar between α- and ß-carboxysomes, remain unknown. Here, we identify C-terminal motifs containing an invariant tryptophan necessary for α- and ß-McdBs to associate with α- and ß-carboxysomes, respectively. Substituting this tryptophan with other aromatic residues reveals corresponding gradients in the efficiency of carboxysome colocalization and positioning by McdB in vivo. Intriguingly, these gradients also correlate with the ability of McdB to form condensates in vitro. The results reveal a shared mechanism underlying McdB adaptor protein binding to carboxysomes, and potentially other BMCs. Our findings also implicate condensate formation as playing a key role in this association.


Assuntos
Proteínas de Bactérias , Triptofano , Triptofano/metabolismo , Proteínas de Bactérias/metabolismo , Organelas/metabolismo , Ciclo do Carbono , Adenosina Trifosfatases/metabolismo , Sequência de Aminoácidos
9.
Biomacromolecules ; 25(7): 4087-4094, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38828905

RESUMO

Living cells, especially eukaryotic ones, use multicompartmentalization to regulate intra- and extracellular activities, featuring membrane-bound and membraneless organelles. These structures govern numerous biological and chemical processes spatially and temporally. Synthetic cell models, primarily utilizing lipidic and polymeric vesicles, have been developed to carry out cascade reactions within their compartments. However, these reconstructions often segregate membrane-bound and membraneless organelles, neglecting their collaborative role in cellular regulation. To address this, we propose a structural design incorporating microfluidic-produced liposomes housing synthetic membrane-bound organelles made from self-assembled poly(ethylene glycol)-block-poly(trimethylene carbonate) nanovesicles and synthetic membraneless organelles formed via temperature-sensitive elastin-like polypeptide phase separation. This architecture mirrors natural cellular organization, facilitating a detailed examination of the interactions for a comprehensive understanding of cellular dynamics.


Assuntos
Células Artificiais , Lipossomos , Organelas , Células Artificiais/química , Organelas/metabolismo , Organelas/química , Lipossomos/química , Polietilenoglicóis/química , Membrana Celular/metabolismo , Membrana Celular/química
10.
Genome Biol Evol ; 16(7)2024 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-38900924

RESUMO

Endosymbiotic relationships have shaped eukaryotic life. As endosymbionts coevolve with their host, toward full integration as organelles, their genomes tend to shrink, with genes being completely lost or transferred to the host nucleus. Modern endosymbionts and organelles show diverse patterns of gene retention, and why some genes and not others are retained in these genomes is not fully understood. Recent bioinformatic study has explored hypothesized influences on these evolutionary processes, finding that hydrophobicity and amino acid chemistry predict patterns of gene retention, both in organelles across eukaryotes and in less mature endosymbiotic relationships. The exciting ongoing elucidation of endosymbiotic relationships affords an independent set of instances to test this theory. Here, we compare the properties of retained genes in the nitroplast, recently reported to be an integrated organelle, two related cyanobacterial endosymbionts that form "spheroid bodies" in their host cells, and a range of other endosymbionts, with free-living relatives of each. We find that in each case, the symbiont's genome encodes proteins with higher hydrophobicity and lower amino pKa than their free-living relative, supporting the data-derived model predicting the retention propensity of genes across endosymbiont and organelle genomes.


Assuntos
Simbiose , Simbiose/genética , Evolução Molecular , Cianobactérias/genética , Filogenia , Interações Hidrofóbicas e Hidrofílicas , Organelas/genética , Genoma Bacteriano
11.
Ecotoxicol Environ Saf ; 281: 116630, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38917590

RESUMO

Benzo[a]pyrene (BaP) is a polycyclic aromatic hydrocarbon compound that is generated during combustion processes, and is present in various substances such as foods, tobacco smoke, and burning emissions. BaP is extensively acknowledged as a highly carcinogenic substance to induce multiple forms of cancer, such as lung cancer, skin cancer, and stomach cancer. Recently it is shown to adversely affect the reproductive system. Nevertheless, the potential toxicity of BaP on oocyte quality remains unclear. In this study, we established a BaP exposure model via mouse oral gavage and found that BaP exposure resulted in a notable decrease in the ovarian weight, number of GV oocytes in ovarian, and oocyte maturation competence. BaP exposure caused ribosomal dysfunction, characterized by a decrease in the expression of RPS3 and HPG in oocytes. BaP exposure also caused abnormal distribution of the endoplasmic reticulum (ER) and induced ER stress, as indicated by increased expression of GRP78. Besides, the Golgi apparatus exhibited an abnormal localization pattern, which was confirmed by the GM130 localization. Disruption of vesicle transport processes was observed by the abnormal expression and localization of Rab10. Additionally, an enhanced lysosome and LC3 fluorescence intensity indicated the occurrence of protein degradation in oocytes. In summary, our results suggested that BaP exposure disrupted the distribution and functioning of organelles, consequently affecting the developmental competence of mouse oocytes.


Assuntos
Benzo(a)pireno , Chaperona BiP do Retículo Endoplasmático , Oócitos , Animais , Benzo(a)pireno/toxicidade , Oócitos/efeitos dos fármacos , Feminino , Camundongos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Retículo Endoplasmático/efeitos dos fármacos , Retículo Endoplasmático/metabolismo , Complexo de Golgi/efeitos dos fármacos , Complexo de Golgi/metabolismo , Organelas/efeitos dos fármacos , Camundongos Endogâmicos ICR
13.
Acc Chem Res ; 57(14): 1906-1917, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-38916405

RESUMO

ConspectusDNA nanodevices are nanoscale assemblies, formed from a collection of synthetic DNA strands, that may perform artificial functions. The pioneering developments of a DNA cube by Nadrian Seeman in 1991 and a DNA nanomachine by Turberfield and Yurke in 2000 spawned an entire generation of DNA nanodevices ranging from minimalist to rococo architectures. Since our first demonstration in 2009 that a DNA nanodevice can function autonomously inside a living cell, it became clear that this molecular scaffold was well-placed to probe living systems. Its water solubility, biocompatibility, and engineerability to yield molecularly identical assemblies predisposed it to probe and program biology.Since DNA is a modular scaffold, one can integrate independent or interdependent functionalities onto a single assembly. Work from our group has established a new class of organelle-targeted, DNA-based fluorescent reporters. These reporters comprise three to four oligonucleotides that each display a specific motif or module with a specific function. Given the 1:1 stoichiometry of Watson-Crick-Franklin base pairing, all modules are present in a fixed ratio in every DNA nanodevice. These modules include an ion-sensitive dye or a detection module and a normalizing dye for ratiometry that along with detection module forms a "measuring module". The third module is an organelle-targeting module that engages a cognate protein so that the whole assembly is trafficked to the lumen of a target organelle. Together, these modules allow us to measure free ion concentrations with accuracies that were previously unattainable, in subcellular locations that were previously inaccessible, and at single organelle resolution. By revealing that organelles exist in different chemical states, DNA nanodevices are providing new insights into organelle biology. Further, the ability to deliver molecules with cell-type and organelle level precision in animal models is leading to biomedical applications.This Account outlines the development of DNA nanodevices as fluorescent reporters for chemically mapping or modulating organelle function in real time in living systems. We discuss the technical challenges of measuring ions within endomembrane organelles and show how the unique properties of DNA nanodevices enable organelle targeting and chemical mapping. Starting from the pioneering finding that an autonomous DNA nanodevice could map endolysosomal pH in cells, we chart the development of strategies to target organelles beyond the endolysosomal pathway and expanding chemical maps to include all the major ions in physiology, reactive species, enzyme activity, and voltage. We present a series of vignettes highlighting the new biology unlocked with each development, from the discovery of chemical heterogeneity in lysosomes to identifying the first protein importer of Ca2+ into lysosomes. Finally, we discuss the broader applicability of targeting DNA nanodevices organelle-specifically beyond just reporting ions, namely using DNA nanodevices to modulate organelle state, and thereby cell state, with potential therapeutic applications.


Assuntos
DNA , Organelas , Organelas/química , Organelas/metabolismo , Humanos , DNA/química , Corantes Fluorescentes/química , Animais , Nanoestruturas/química
14.
Proc Natl Acad Sci U S A ; 121(25): e2322588121, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38861598

RESUMO

The nematode intestine is the primary site for nutrient uptake and storage as well as the synthesis of biomolecules; lysosome-related organelles known as gut granules are important for many of these functions. Aspects of intestine biology are not well understood, including the export of the nutrients it imports and the molecules it synthesizes, as well as the complete functions and protein content of the gut granules. Here, we report a mass spectrometry (MS)-based proteomic analysis of the intestine of the Caenorhabditis elegans and of its gut granules. Overall, we identified approximately 5,000 proteins each in the intestine and the gonad and showed that most of these proteins can be detected in samples extracted from a single worm, suggesting the feasibility of individual-level genetic analysis using proteomes. Comparing proteomes and published transcriptomes of the intestine and the gonad, we identified proteins that appear to be synthesized in the intestine and then transferred to the gonad. To identify gut granule proteins, we compared the proteome of individual intestines deficient in gut granules to the wild type. The identified gut granule proteome includes proteins known to be exclusively localized to the granules and additional putative gut granule proteins. We selected two of these putative gut granule proteins for validation via immunohistochemistry, and our successful confirmation of both suggests that our strategy was effective in identifying the gut granule proteome. Our results demonstrate the practicability of single-tissue MS-based proteomic analysis in small organisms and in its future utility.


Assuntos
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Lisossomos , Proteômica , Animais , Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteômica/métodos , Lisossomos/metabolismo , Proteoma/metabolismo , Intestinos , Mucosa Intestinal/metabolismo , Gônadas/metabolismo , Espectrometria de Massas/métodos , Organelas/metabolismo
15.
Methods Mol Biol ; 2800: 231-244, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38709488

RESUMO

In this chapter, we describe protocols for using the CellOrganizer software on the Jupyter Notebook platform to analyze and model cell and organelle shape and spatial arrangement. CellOrganizer is an open-source system for using microscope images to learn statistical models of the structure of cell components and how those components are organized relative to each other. Such models capture the statistical variation in the organization of cellular components by jointly modeling the distributions of their number, shape, and spatial distributions. These models can be created for different cell types or conditions and compared to reflect differences in their spatial organizations. The models are also generative, in that they can be used to synthesize new cell instances reflecting what a model learned and to provide well-structured cell geometries that can be used for biochemical simulations.


Assuntos
Software , Processamento de Imagem Assistida por Computador/métodos , Modelos Biológicos , Humanos , Simulação por Computador , Organelas/metabolismo
16.
Methods Mol Biol ; 2807: 113-125, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38743224

RESUMO

The postnuclear entry steps of HIV-1 involve reverse transcription, uncoating, and integration into the host genome. The differential regulation of these steps has a significant impact on HIV overall replication, including integration site selection and viral gene expression. Recently, another important phenomenon has been uncovered as part of HIV interplay with the nuclear environment, specifically involving the cleavage and polyadenylation specific factor 6 (CPSF6) protein. This phenomenon is the formation of nuclear HIV-induced membraneless organelles (HIV-1 MLOs). In this article, we will describe the methods used to assess the composition and liquid-liquid phase separation (LLPS) properties of these organelles using fluorescence microscopy. The study of HIV-1 MLOs represents a new frontier that may reveal previously unknown key players in the fate of HIV-infected cells.


Assuntos
Núcleo Celular , HIV-1 , Microscopia de Fluorescência , Humanos , Microscopia de Fluorescência/métodos , HIV-1/fisiologia , HIV-1/genética , Núcleo Celular/metabolismo , Organelas/metabolismo , Infecções por HIV/virologia , Infecções por HIV/metabolismo
17.
Rev Assoc Med Bras (1992) ; 70(5): e20231337, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38775506

RESUMO

OBJECTIVE: It has been previously shown that brain-derived neurotrophic factor is linked with various types of cancer. Brain-derived neurotrophic factor is found to be highly expressed in multiple human cancers and associated with tumor growth, invasion, and metastasis. Adipokinetic hormones are functionally related to the vertebrate glucagon, as they have similar functionalities that manage the nutrient-dependent secretion of these two hormones. Migrasomes are new organelles that contain numerous small vesicles, which aid in transmitting signals between the migrating cells. Therefore, the aim of this study was to investigate the effects of Anax imperator adipokinetic hormone on brain-derived neurotrophic factor expression and ultrastructure of cells in the C6 glioma cell line. METHODS: The rat C6 glioma cells were treated with concentrations of 5 and 10 Anax imperator adipokinetic hormone for 24 h. The effects of the Anax imperator adipokinetic hormone on the migrasome formation and brain-derived neurotrophic factor expression were analyzed using immunocytochemistry and transmission electron microscope. RESULTS: The rat C6 glioma cells of the 5 and 10 µM Anax imperator adipokinetic hormone groups showed significantly high expressions of brain-derived neurotrophic factor and migrasomes numbers, compared with the control group. CONCLUSION: A positive correlation was found between the brain-derived neurotrophic factor expression level and the formation of migrasome, which indicates that the increased expression of brain-derived neurotrophic factor and the number of migrasomes may be involved to metastasis of the rat C6 glioma cell line induced by the Anax imperator adipokinetic hormone. Therefore, the expression of brain-derived neurotrophic factor and migrasome formation may be promising targets for preventing tumor proliferation, invasion, and metastasis in glioma.


Assuntos
Fator Neurotrófico Derivado do Encéfalo , Glioma , Oligopeptídeos , Ácido Pirrolidonocarboxílico , Glioma/metabolismo , Glioma/patologia , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Ratos , Linhagem Celular Tumoral , Ácido Pirrolidonocarboxílico/análogos & derivados , Ácido Pirrolidonocarboxílico/metabolismo , Oligopeptídeos/farmacologia , Hormônios de Inseto/metabolismo , Movimento Celular/efeitos dos fármacos , Imuno-Histoquímica , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Organelas/metabolismo , Organelas/efeitos dos fármacos , Organelas/ultraestrutura
18.
J Cell Biol ; 223(7)2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38748249

RESUMO

Bacteria, omnipresent in our environment and coexisting within our body, exert dual beneficial and pathogenic influences. These microorganisms engage in intricate interactions with the human body, impacting both human health and disease. Simultaneously, certain organelles within our cells share an evolutionary relationship with bacteria, particularly mitochondria, best known for their energy production role and their dynamic interaction with each other and other organelles. In recent years, communication between bacteria and mitochondria has emerged as a new mechanism for regulating the host's physiology and pathology. In this review, we delve into the dynamic communications between bacteria and host mitochondria, shedding light on their collaborative regulation of host immune response, metabolism, aging, and longevity. Additionally, we discuss bacterial interactions with other organelles, including chloroplasts, lysosomes, and the endoplasmic reticulum (ER).


Assuntos
Bactérias , Interações Hospedeiro-Patógeno , Mitocôndrias , Animais , Humanos , Bactérias/metabolismo , Retículo Endoplasmático/metabolismo , Retículo Endoplasmático/microbiologia , Lisossomos/metabolismo , Lisossomos/microbiologia , Mitocôndrias/metabolismo , Organelas/metabolismo
19.
Int Rev Neurobiol ; 176: 455-479, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38802180

RESUMO

Amyotrophic lateral sclerosis (ALS) and related neurodegenerative diseases are characterised by dysfunction of a host of RNA-binding proteins (RBPs) and a severely disrupted RNA metabolism. Recently, RBP-harbouring phase-separated complexes, ribonucleoprotein (RNP) granules, have come into the limelight as "crucibles" of neuronal pathology in ALS. RNP granules are indispensable for the multitude of regulatory processes underlying cellular RNA metabolism and serve as critical organisers of cellular biochemistry. Neurons, highly specialised cells, heavily rely on RNP granules for efficient trafficking, signalling and stress responses. Multiple RNP granule components, primarily RBPs such as TDP-43 and FUS, are affected by ALS mutations. However, even in the absence of mutations, RBP proteinopathies represent pathophysiological hallmarks of ALS. Given the high local concentrations of RBPs and RNAs, their weakened or enhanced interactions within RNP granules disrupt their homeostasis. Thus, the physiological process of phase separation and RNP granule formation, vital for maintaining the high-functioning state of neuronal cells, becomes their Achilles heel. Here, we will review the recent literature on the causes and consequences of abnormal RNP granule functioning in ALS and related disorders. In particular, we will summarise the evidence for the network-level dysfunction of RNP granules in these conditions and discuss considerations for therapeutic interventions to target RBPs, RNP granules and their network as a whole.


Assuntos
Esclerose Lateral Amiotrófica , Grânulos Citoplasmáticos , Ribonucleoproteínas , Humanos , Esclerose Lateral Amiotrófica/metabolismo , Esclerose Lateral Amiotrófica/patologia , Ribonucleoproteínas/metabolismo , Animais , Grânulos Citoplasmáticos/metabolismo , Doenças Neurodegenerativas/metabolismo , Organelas/metabolismo
20.
PLoS Biol ; 22(5): e3002608, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38713727

RESUMO

Algae and plants carry 2 organelles of endosymbiotic origin that have been co-evolving in their host cells for more than a billion years. The biology of plastids and mitochondria can differ significantly across major lineages and organelle changes likely accompanied the adaptation to new ecological niches such as the terrestrial habitat. Based on organelle proteome data and the genomes of 168 phototrophic (Archaeplastida) versus a broad range of 518 non-phototrophic eukaryotes, we screened for changes in plastid and mitochondrial biology across 1 billion years of evolution. Taking into account 331,571 protein families (or orthogroups), we identify 31,625 protein families that are unique to primary plastid-bearing eukaryotes. The 1,906 and 825 protein families are predicted to operate in plastids and mitochondria, respectively. Tracing the evolutionary history of these protein families through evolutionary time uncovers the significant remodeling the organelles experienced from algae to land plants. The analyses of gained orthogroups identifies molecular changes of organelle biology that connect to the diversification of major lineages and facilitated major transitions from chlorophytes en route to the global greening and origin of angiosperms.


Assuntos
Magnoliopsida , Proteínas Mitocondriais , Filogenia , Plastídeos , Plastídeos/metabolismo , Plastídeos/genética , Magnoliopsida/genética , Magnoliopsida/metabolismo , Proteínas Mitocondriais/metabolismo , Proteínas Mitocondriais/genética , Evolução Molecular , Evolução Biológica , Mitocôndrias/metabolismo , Mitocôndrias/genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Proteoma/metabolismo , Simbiose/genética , Organelas/metabolismo , Organelas/genética
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