{"title":"Lipid transfer at mitochondrial membrane contact sites","authors":"Qingzhu Chu , Wei-Ke Ji","doi":"10.1016/j.mitoco.2024.11.002","DOIUrl":"10.1016/j.mitoco.2024.11.002","url":null,"abstract":"<div><div>Mitochondria are semiautonomous organelles that are actively shaped into an extended reticular network that is not connected to the endomembrane system via vesicular transport. Instead, active lipid exchange occurs between mitochondria and other organelles, such as the endoplasmic reticulum (ER) and lipid droplets (LDs), at mitochondrial membrane contact sites (MCSs), where the two organelles are juxtaposed with each other at a distance of 10–30 nm. Recent advances have led to an increasing understanding of the molecular mechanism that mediates the transfer of different lipid species between these organelles. Here, we highlight advances that demonstrate the role of lipid transfer proteins at ER–mitochondrial and LD–mitochondrial MCSs. Importantly, we summarize the fundamental questions on this topic that remain unanswered.</div></div>","PeriodicalId":100931,"journal":{"name":"Mitochondrial Communications","volume":"2 ","pages":"Pages 123-128"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143143975","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}
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 , Xiangwaner Jin , Yi Zhang , Yanan Li, Jinming Liu, 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}
{"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}
{"title":"The mitochondria chronicles of melatonin and ATP: Guardians of phase separation","authors":"Doris Loh , 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}
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 , Alfredo Cruz-Gregorio , Isabel Amador-Martínez , Estefani Yaquelin Hernández-Cruz , Edilia Tapia , 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}
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 , Douglas C. Wallace , 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}
{"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}
{"title":"Defective biogenesis of human mitochondrial ribosomes causes sensorineural deafness","authors":"Chao Chen Ph.D. , Wenqi Shan , 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 > G and 1494C > 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 > G and TRMU c.28G > T mutations displayed greater defects in the morphology and functions than those in cells bearing only m.1555A > G mutation and these defects were restored by genetic correction of TRMU c.28G > 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}
María de los Angeles Carcamo , Rodrigo A. Quintanilla , William Tiznado , Lina M. Ruiz
{"title":"Sex differences in the genetics of autism spectrum disorder and their impact on gene expression associated with mitochondrial function","authors":"María de los Angeles Carcamo , Rodrigo A. Quintanilla , William Tiznado , Lina M. Ruiz","doi":"10.1016/j.mitoco.2024.12.001","DOIUrl":"10.1016/j.mitoco.2024.12.001","url":null,"abstract":"<div><div>Autism spectrum disorder (ASD) is a neurodevelopmental condition that affects social-communicative skills and is characterized by restricted and stereotyped behaviors. It affects more males, with a ratio of 4:1, and has a prevalence of 1:54 children. Manifestations of ASD vary by gender, with specific behaviors less pronounced in females. Using data from the Gene Expression Omnibus repository, this research explored sex-related genetic differences in ASD and their impact on mitochondrial gene expression. Peripheral blood DNA was found to exhibit differential methylation patterns by sex, with additional alterations in individuals with ASD. Sex-specific transcriptional changes were also identified in cord blood from high-risk ASD pregnancies. Of 50 genes with differential methylation by sex, only the <em>PLEKHN1</em> gene is related to mitochondrial function. Age correlated with symptoms and diagnosis in males, whereas <em>PLEKHN1</em> methylation was associated with age and internalizing symptoms in females. In conclusion, sex influences genetic contributions in ASD, affecting mitochondrial gene expression.</div></div>","PeriodicalId":100931,"journal":{"name":"Mitochondrial Communications","volume":"2 ","pages":"Pages 129-139"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143143973","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}