Mitochondrial Communications最新文献

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Tissue-specific knockdown of OMM protein via GFP nanobody-mediated degradation 通过 GFP 纳米抗体介导的降解,特异性敲除组织中的 OMM 蛋白
Mitochondrial Communications Pub Date : 2024-01-01 DOI: 10.1016/j.mitoco.2024.07.003
Xiaojie Wang , Qiyue Zhang , Suhong Xu
{"title":"Tissue-specific knockdown of OMM protein via GFP nanobody-mediated degradation","authors":"Xiaojie Wang ,&nbsp;Qiyue Zhang ,&nbsp;Suhong Xu","doi":"10.1016/j.mitoco.2024.07.003","DOIUrl":"10.1016/j.mitoco.2024.07.003","url":null,"abstract":"<div><p>Mitochondria, with their diverse morphologies across tissues, hint at a unique function based on location. For instance, outer mitochondrial membrane (OMM) proteins are critical for various mitochondrial activities, including regulating mitochondrial dynamics, ion homeostasis, and protein translocation. This study introduces a green fluorescent protein (GFP) nanobody-mediated protein degradation (G-DEG) system to investigate tissue-specific mitochondrial functions in <em>Caenorhabditis elegans</em> and potential other model systems. G-DEG combines CRISPR-Cas9 GFP knock-in with ZIF-1-mediated protein degradation, leveraging the high specificity of antigen–antibody recognition for precise manipulation across species. We demonstrate the G-DEG system by targeting FZO-1, a mammalian homolog of MAN1/2, which is essential for mitochondrial fusion. Our protocol includes CRISPR-Cas9-mediated <em>fzo-1</em>:GFP knock-in and the construction of tissue-specific GFP nanobody degradation plasmids for the epidermis, muscle, and neurons. Injection of these plasmids into wild-type <em>C. elegans</em> and subsequent crossbreeding with the <em>fzo-1</em>:GFP knock-in strain allows for effective FZO-1 targeting, providing tissue-specific insights into mitochondrial protein function. Overall, G-DEG emerges as a powerful and versatile tool for tissue-specific knockdown of OMM proteins, paving the way for advanced studies on their diverse biological functions.</p></div>","PeriodicalId":100931,"journal":{"name":"Mitochondrial Communications","volume":"2 ","pages":"Pages 85-89"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590279224000087/pdfft?md5=f5d2d52b3e5d9bb6460686031c07f0e6&pid=1-s2.0-S2590279224000087-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141961581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Single-cell mitochondrial DNA sequencing: Methodologies and applications 单细胞线粒体 DNA 测序:方法与应用
Mitochondrial Communications Pub Date : 2024-01-01 DOI: 10.1016/j.mitoco.2024.10.001
Guoqiang Zhou , Zhenglong Gu , Jin Xu
{"title":"Single-cell mitochondrial DNA sequencing: Methodologies and applications","authors":"Guoqiang Zhou ,&nbsp;Zhenglong Gu ,&nbsp;Jin Xu","doi":"10.1016/j.mitoco.2024.10.001","DOIUrl":"10.1016/j.mitoco.2024.10.001","url":null,"abstract":"<div><div>Mitochondria play a pivotal role in cellular energetics, metabolism, and various regulatory processes. Their dysregulation is implicated in numerous diseases. Traditional population-level mitochondrial DNA (mtDNA) sequencing often obscures crucial information from individual cells, leading to a limited understanding of mitochondrial genetics. In contrast, single-cell mtDNA sequencing enables the precise detection and characterization of mtDNA mutations at the individual cell level, providing a nuanced view of mitochondrial heteroplasmy and its dynamics. This review aims to provide a comprehensive overview of current single-cell mtDNA sequencing methodologies and their applications in advancing our understanding of mitochondrial genetics.</div></div>","PeriodicalId":100931,"journal":{"name":"Mitochondrial Communications","volume":"2 ","pages":"Pages 107-113"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142571269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Innovative methods for isolating highly purified mitochondria essential for biomedical studies 分离生物医学研究必需的高纯度线粒体的创新方法
Mitochondrial Communications Pub Date : 2024-01-01 DOI: 10.1016/j.mitoco.2024.09.002
Yan Huang , Xiangwaner Jin , Yi Zhang , Yanan Li, Jinming Liu, Yanjun Li
{"title":"Innovative methods for isolating highly purified mitochondria essential for biomedical studies","authors":"Yan Huang ,&nbsp;Xiangwaner Jin ,&nbsp;Yi Zhang ,&nbsp;Yanan Li,&nbsp;Jinming Liu,&nbsp;Yanjun Li","doi":"10.1016/j.mitoco.2024.09.002","DOIUrl":"10.1016/j.mitoco.2024.09.002","url":null,"abstract":"<div><div>Mitochondria, being multifunctional and highly complex organelles, possess unique structures and exhibit heterogeneity. In recent decades, the isolation and purification of functional mitochondria have been instrumental for mitochondrial research. As mitochondrial research, including omics, advances, there is a growing demand for the isolation of highly purified mitochondria or individual mitochondria. This paper provides a comprehensive overview of the evolution of mitochondrial purification methods and introduces two innovative and improved techniques for isolating mitochondria from mouse cerebral cortex and in vitro cultured cells. The first method utilizes self-prepared magnetic beads conjugated with anti-TOMM20 antibody for the immunoisolation of highly purified intact mitochondria. The second method utilizes flow cytometry to isolate single mitochondria based on fluorescent protein labeling, allowing for the isolation of mitochondria from a highly heterogeneous population. We provide detailed protocols that aim to benefit the rapidly growing mitochondria research community in assessing mitochondrial function, especially at the single-organelle level.</div></div>","PeriodicalId":100931,"journal":{"name":"Mitochondrial Communications","volume":"2 ","pages":"Pages 90-99"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142423696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mitochondrial lipid metabolism in metastatic breast cancer 转移性乳腺癌的线粒体脂质代谢
Mitochondrial Communications Pub Date : 2024-01-01 DOI: 10.1016/j.mitoco.2024.07.001
Bhuban Ruidas
{"title":"Mitochondrial lipid metabolism in metastatic breast cancer","authors":"Bhuban Ruidas","doi":"10.1016/j.mitoco.2024.07.001","DOIUrl":"10.1016/j.mitoco.2024.07.001","url":null,"abstract":"<div><p>The significance of mitochondrial lipid metabolism in cancer stemness, survival, and proliferation, particularly in the context of metastasis, has garnered significant attention. Warburg's hypothesis posits that cancer cells primarily rely on aerobic glycolysis for survival due to mitochondrial dysfunction. However, recent evidence has challenged this perspective, emphasizing the direct involvement of mitochondria in cancer's rapid progression. Metabolic rearrangements, a hallmark of metastatic cancer, fulfill heightened energy demands during rapid proliferation, primarily through mitochondrial oxidative phosphorylation and lipid metabolism, even under hypoxic conditions. Moreover, lipid metabolism is elevated throughout the progression of metastatic cancer to meet crucial energy needs. However, the relative importance of mitochondrial lipid metabolism and aerobic glycolysis in highly aggressive cancers remains poorly defined, and further investigation could enhance treatment outcomes in cases of metastatic progression. In this context, a comprehensive understanding of mitochondrial lipid metabolism in metastatic breast cancer patients could potentially lead to significant breakthroughs in improving therapies, especially for triple-negative breast cancer.</p></div>","PeriodicalId":100931,"journal":{"name":"Mitochondrial Communications","volume":"2 ","pages":"Pages 58-66"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590279224000063/pdfft?md5=50183d4ee164426611eb75a5606347dd&pid=1-s2.0-S2590279224000063-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141843364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The mitochondria chronicles of melatonin and ATP: Guardians of phase separation 褪黑素和 ATP 的线粒体编年史:相分离的守护者
Mitochondrial Communications Pub Date : 2024-01-01 DOI: 10.1016/j.mitoco.2024.07.002
Doris Loh , Russel J. Reiter
{"title":"The mitochondria chronicles of melatonin and ATP: Guardians of phase separation","authors":"Doris Loh ,&nbsp;Russel J. Reiter","doi":"10.1016/j.mitoco.2024.07.002","DOIUrl":"10.1016/j.mitoco.2024.07.002","url":null,"abstract":"<div><p>Phase separation is a thermodynamic process used by all living organisms since the origin of life to rapidly assemble and disassemble membraneless condensates in response to changes in exogenous and endogenous stress conditions. For ∼4.5 billion years, living organisms in the three major domains of life depended upon the high chemical potential of adenosine triphosphate (ATP) to harness nonequilibrium chemical reactions that govern the formation and suppression of membraneless organelles via phase separation. Melatonin enhances the unique chemistry of ATP in water, promoting the solubilization via the adenosine moiety effect, supporting the survival of early organisms in an anoxic environment. Eukaryotes, including dinoflagellates and plants, can produce melatonin in extreme levels under stress as compensation for inadequate ATP for optimal regulation of survival responses dependent upon phase separation. The production of ATP and melatonin in mitochondria enables the fine-tuning of dynamics that modulate phase separation of proteins associated with ATP production, biogenesis and degradation, membrane dynamics, gene transcription, mitophagy, unfolded protein response, and apoptosis/survival responses in mitochondria. Exogenous melatonin application enhances mitochondrial ATP production and synergy, attenuating aberrant phase separation and associated mitochondrial dysfunction and disease.</p></div>","PeriodicalId":100931,"journal":{"name":"Mitochondrial Communications","volume":"2 ","pages":"Pages 67-84"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590279224000075/pdfft?md5=7d5edc08bd32f09b779eb9636af81ee8&pid=1-s2.0-S2590279224000075-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141846938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Antioxidants targeting mitochondria function in kidney diseases 针对肾脏疾病线粒体功能的抗氧化剂
Mitochondrial Communications Pub Date : 2024-01-01 DOI: 10.1016/j.mitoco.2024.03.002
Ana Karina Aranda-Rivera , Alfredo Cruz-Gregorio , Isabel Amador-Martínez , Estefani Yaquelin Hernández-Cruz , Edilia Tapia , José Pedraza-Chaverri
{"title":"Antioxidants targeting mitochondria function in kidney diseases","authors":"Ana Karina Aranda-Rivera ,&nbsp;Alfredo Cruz-Gregorio ,&nbsp;Isabel Amador-Martínez ,&nbsp;Estefani Yaquelin Hernández-Cruz ,&nbsp;Edilia Tapia ,&nbsp;José Pedraza-Chaverri","doi":"10.1016/j.mitoco.2024.03.002","DOIUrl":"https://doi.org/10.1016/j.mitoco.2024.03.002","url":null,"abstract":"<div><p>Kidney diseases are a growing health problem worldwide, causing millions of deaths. Acute kidney injury (AKI) commonly evolves into chronic kidney disease (CKD) and fibrosis, which is a feature of CKD predisposing to end-stage renal disease. Thus, treatments that avoid this transition are urgently necessary. Mitochondria are the hub energy house of the renal cells, which provides energy in adenosine triphosphate (ATP) form, commonly obtained from β-oxidation through fatty acids degradation into the mitochondrial matrix. Mitochondria are plastic organelles that constantly change according to the cell's energy requirements. For this, mitochondria carry out biogenesis, fission, fusion, and mitophagy/autophagy, processes highly regulated to maintain mitochondrial bioenergetics and homeostasis. Alterations in one or more of these processes might cause detrimental consequences that affect cell function. In this sense, it is widely accepted that mitochondrial dysfunction associated with oxidative stress plays a crucial role in developing kidney diseases. Therefore, antioxidants that target mitochondria might be an excellent strategy to ameliorate mitochondrial dysfunction, and selecting one or another antioxidant could depend on AKI or CKD requirements. This review focuses on potent antioxidants such as sulforaphane (SFN), <em>N</em>-acetyl cysteine (NAC), resveratrol, curcumin, quercetin, and α-mangostin in the improvement of mitochondrial function in kidney pathologies.</p></div>","PeriodicalId":100931,"journal":{"name":"Mitochondrial Communications","volume":"2 ","pages":"Pages 21-37"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S259027922400004X/pdfft?md5=5869184899ade6f79d140563bae21bc8&pid=1-s2.0-S259027922400004X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140327839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Photobleaching and phototoxicity of mitochondria in live cell fluorescent super-resolution microscopy 活细胞荧光超分辨率显微镜中线粒体的光漂白和光毒性
Mitochondrial Communications Pub Date : 2024-01-01 DOI: 10.1016/j.mitoco.2024.03.001
Chia-Hung Lee , Douglas C. Wallace , Peter J. Burke
{"title":"Photobleaching and phototoxicity of mitochondria in live cell fluorescent super-resolution microscopy","authors":"Chia-Hung Lee ,&nbsp;Douglas C. Wallace ,&nbsp;Peter J. Burke","doi":"10.1016/j.mitoco.2024.03.001","DOIUrl":"10.1016/j.mitoco.2024.03.001","url":null,"abstract":"<div><p>Photobleaching and phototoxicity can induce detrimental effects on cell viability and compromise the integrity of collected data, particularly in studies utilizing super-resolution microscopes. Given the involvement of multiple factors, it is currently challenging to propose a single set of standards for assessing the potential of phototoxicity. The objective of this paper is to present empirical data on the effects of photobleaching and phototoxicity on mitochondria during super-resolution imaging of mitochondrial structure and function using Airyscan and the fluorescent structure dyes Mitotracker green (MTG), 10-N-nonyl acridine orange (NAO), and voltage dye Tetramethylrhodamine, Ethyl Ester (TMRE). We discern two related phenomena. First, phototoxicity causes a transformation of mitochondria from tubular to spherical shape, accompanied by a reduction in the number of cristae. Second, phototoxicity impacts the mitochondrial membrane potential. Through these parameters, we discovered that upon illumination, NAO is much more phototoxic to mitochondria compared to MTG or TMRE and that these parameters can be used to evaluate the relative phototoxicity of various mitochondrial dye-illumination combinations during mitochondrial imaging.</p></div>","PeriodicalId":100931,"journal":{"name":"Mitochondrial Communications","volume":"2 ","pages":"Pages 38-47"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590279224000038/pdfft?md5=96dab14e2fc33e7b9392f96865841292&pid=1-s2.0-S2590279224000038-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140275628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Is localized chemiosmosis necessary in mitochondria? Is Lee's TELP protonic capacitor hypothesis a reasonable model? 线粒体中的局部化合作用是否必要?李的 TELP 质子电容器假说是一个合理的模型吗?
Mitochondrial Communications Pub Date : 2024-01-01 DOI: 10.1016/j.mitoco.2024.06.001
Todd P. Silverstein
{"title":"Is localized chemiosmosis necessary in mitochondria? Is Lee's TELP protonic capacitor hypothesis a reasonable model?","authors":"Todd P. Silverstein","doi":"10.1016/j.mitoco.2024.06.001","DOIUrl":"https://doi.org/10.1016/j.mitoco.2024.06.001","url":null,"abstract":"<div><p>Recent high-resolution pH measurements in mitochondria show ΔpH across the F<sub>1</sub>F<sub>0</sub> ATP synthase to be quite low, 0.07–0.32. Our meta-analysis of published values of transmembrane potential (<span><math><mrow><mo>Δ</mo><mi>ψ</mi></mrow></math></span>) shows it to be identical in vivo and in vitro: -159 ± 16 mV. With the low ΔpH, the thermodynamic efficiency of proton-driven ATP synthesis exceeds 100 % for average- and low-potential (−123 mV) mitochondria, and possibly also for high-potential (−180 mV) mitochondria. Efficiencies exceeding 100 % may violate the second law of thermodynamics, and suggest a need for localized chemiosmosis, i.e., the existence of a membrane surface ΔpH that exceeds the bulk phase ΔpH by at least 0.2 units in high-potential mitochondria, and by 1.1 units in low-potential mitochondria. The lack of equilibration between protons in the bulk phase and those at the membrane surface is explained by two models which we discuss and compare: the potential well/barrier model, and the TELP protonic capacitor model.</p></div>","PeriodicalId":100931,"journal":{"name":"Mitochondrial Communications","volume":"2 ","pages":"Pages 48-57"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590279224000051/pdfft?md5=ed06f95ee11648d4c7f30933cafa6792&pid=1-s2.0-S2590279224000051-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141303240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Defective biogenesis of human mitochondrial ribosomes causes sensorineural deafness 人类线粒体核糖体生物生成缺陷导致感音神经性耳聋
Mitochondrial Communications Pub Date : 2024-01-01 DOI: 10.1016/j.mitoco.2024.11.001
Chao Chen Ph.D. , Wenqi Shan , Min-Xin Guan Ph.D.
{"title":"Defective biogenesis of human mitochondrial ribosomes causes sensorineural deafness","authors":"Chao Chen Ph.D. ,&nbsp;Wenqi Shan ,&nbsp;Min-Xin Guan Ph.D.","doi":"10.1016/j.mitoco.2024.11.001","DOIUrl":"10.1016/j.mitoco.2024.11.001","url":null,"abstract":"<div><div>Thirteen proteins of oxidative phosphorylation complexes encoded by mitochondrial DNA (mtDNA) were synthesized by own specific ribosomes (mitoribosomes). Mitoribosomes composed of nucleus-encoding proteins and mtDNA-encoding 12S and 16S ribosomal RNA. They are linked with sensorineural deafness and the targets of aminoglycosides. Mutations in nuclear genes encoding mitoribosome subunits cause syndromic deafness. The 12S rRNA 1555A &gt; G and 1494C &gt; T mutations have been associated with aminoglycoside-induced and nonsyndromic deafness in many families worldwide. These mutations create 1494C-G1555 or 1494U-A1555 base-pair at the A-site of 12S rRNA, make ribosomes more bacteria-like, thereby altering the binding for aminoglycosides and translation. These mutations conferred to mild mitochondrial dysfunctions, thereby requiring genetic and environmental factors to produce a deafness phenotype. The administration of aminoglycosides induces deafness in these subjects carrying the 12S rRNA mutations. Nuclear modifier including TRMU and mitochondrial modifier contributed to the tissue-specific phenotypic manifestation of 12S rRNA mutations. Especially, hair cell-like cells differentiated from patients-derived iPSCs harboring both m.1555A &gt; G and TRMU c.28G &gt; T mutations displayed greater defects in the morphology and functions than those in cells bearing only m.1555A &gt; G mutation and these defects were restored by genetic correction of TRMU c.28G &gt; T mutation. These provide new insights into pathophysiology of deafness, genetic counseling, prevention and therapeutic interventions for this disease.</div></div>","PeriodicalId":100931,"journal":{"name":"Mitochondrial Communications","volume":"2 ","pages":"Pages 114-122"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142706268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Structural determinants of mitochondrial STAT3 targeting and function 线粒体 STAT3 靶向和功能的结构决定因素
Mitochondrial Communications Pub Date : 2024-01-01 DOI: 10.1016/j.mitoco.2024.01.001
Isabelle J. Marié , Tanaya Lahiri , Özlem Önder , Kojo S.J. Elenitoba-Johnson , David E. Levy
{"title":"Structural determinants of mitochondrial STAT3 targeting and function","authors":"Isabelle J. Marié ,&nbsp;Tanaya Lahiri ,&nbsp;Özlem Önder ,&nbsp;Kojo S.J. Elenitoba-Johnson ,&nbsp;David E. Levy","doi":"10.1016/j.mitoco.2024.01.001","DOIUrl":"10.1016/j.mitoco.2024.01.001","url":null,"abstract":"<div><p>Signal transducer and activator of transcription (STAT) 3 has been found within mitochondria in addition to its canonical role of shuttling between cytoplasm and nucleus during cytokine signaling. Mitochondrial STAT3 has been implicated in modulation of cellular metabolism, largely through effects on the respiratory electron transport chain. However, the structural requirements underlying mitochondrial targeting and function have remained unclear. Here, we show that mitochondrial STAT3 partitions between mitochondrial compartments defined by differential detergent solubility, suggesting that mitochondrial STAT3 is membrane associated. The majority of STAT3 was found in an SDS soluble fraction copurifying with respiratory chain proteins, including numerous components of the complex I NADH dehydrogenase, while a minor component was found with proteins of the mitochondrial translation machinery. Mitochondrial targeting of STAT3 required the amino-terminal domain, and an internal linker domain motif also directed mitochondrial translocation. However, neither the phosphorylation of serine 727 nor the presence of mitochondrial DNA was required for the mitochondrial localization of STAT3. Two cysteine residues in the STAT3 SH2 domain, which have been previously suggested to be targets for protein palmitoylation, were also not required for mitochondrial translocation, but were required for its function as an enhancer of complex I activity. These structural determinants of STAT3 mitochondrial targeting and function provide potential therapeutic targets for disrupting the activity of mitochondrial STAT3 in diseases such as cancer.</p></div>","PeriodicalId":100931,"journal":{"name":"Mitochondrial Communications","volume":"2 ","pages":"Pages 1-13"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590279224000014/pdfft?md5=0cbb61fa14ca122b7f046fd145ac06aa&pid=1-s2.0-S2590279224000014-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139455625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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