Journal of World Mitochondria Society最新文献_第4页

Cytochrome c release: A mitochondrial predictor of post-ischemic cardiac graft recovery in donation after circulatory death 细胞色素c释放:血液循环死亡后捐献的缺血心脏移植恢复的线粒体预测因子

Journal of World Mitochondria Society Pub Date : 2016-09-26 DOI: 10.18143/JWMS_v2i2_1940

R. Wyss, N. M. Carmona, H. T. Stahel, S. Longnus

{"title":"Cytochrome c release: A mitochondrial predictor of post-ischemic cardiac graft recovery in donation after circulatory death","authors":"R. Wyss, N. M. Carmona, H. T. Stahel, S. Longnus","doi":"10.18143/JWMS_v2i2_1940","DOIUrl":"https://doi.org/10.18143/JWMS_v2i2_1940","url":null,"abstract":"Objectives: In cardiac ischemia-reperfusion, mitochondrial damage is determinant in cellular survival. Ischemia-reperfusion injury is a major concern for graft quality in heart transplantation with donation after circulatory death (DCD). Therefore, we investigated whether release of cytochrome c by cardiac mitochondria could be used as an early biomarker of hemodynamic recovery in an isolated rat heart model of DCD. Methodology: Isolated working rat hearts underwent 21, 24, 27, 30, or 33 min warm, global ischemia followed by 60 min reperfusion. Left ventricular work (developed pressure-heart rate product) was monitored with an intraventricular pressure catheter. Coronary effluent was collected at 10 minutes of reperfusion for measurement of cytochrome c and lactate using commercially available kits. Results: Compared with non-ischemic controls, cytochrome c release was 2-fold higher after 21 min ischemia and increased progressively with ischemic duration to reaching a 10-fold elevation after 33 min ischemia. Cytochrome c and lactate release inversely correlated with post-ischemic left ventricular work (r=-0.81, p<0.001 and r=-0.46, p<0.01, respectively). Conclusion: Cytochrome c is a sensitive, early predictor of cardiac hemodynamic recovery that can be measured easily and rapidly. Cytochrome c could be useful for evaluation of DCD cardiac grafts for transplantation in addition to the currently used lactate.","PeriodicalId":266249,"journal":{"name":"Journal of World Mitochondria Society","volume":"32 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115709828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Does polyribonucleotide nucleotidyltransferase (PNPase) mutation affect the energetic metabolism and the microRNA profile in cell and mitochondria 多核糖核苷酸核苷酸转移酶(PNPase)突变是否影响细胞和线粒体的能量代谢和microRNA谱

Journal of World Mitochondria Society Pub Date : 2016-09-23 DOI: 10.18143/JWMS_V2I2_1980

E. Barrey, M. Beinat, L. Moyec, A. Rötig

{"title":"Does polyribonucleotide nucleotidyltransferase (PNPase) mutation affect the energetic metabolism and the microRNA profile in cell and mitochondria","authors":"E. Barrey, M. Beinat, L. Moyec, A. Rötig","doi":"10.18143/JWMS_V2I2_1980","DOIUrl":"https://doi.org/10.18143/JWMS_V2I2_1980","url":null,"abstract":"Objectives PNPase is a protein of the intermembrane space, encoded by PNPT1 and involved in RNA mitochondrial import [1]. PNPT1 mutations have been described in patients suffering from a severe neurological disease and combined respiratory chain defect [2]. We hypothesized that PNPAse could play a role in miRNA import [3]. The objective was to compare the miRNA and metabolomic profile from control and PNPT1 mutant fibroblasts. Methodology and Results Fibroblasts from a patient with PNPT1 mutation (c.1160A>G, p.Gln387Arg) and from a control (C) were grown. Comparison of the metabolomic NMR spectra of their culture media suggested that PNPT1 cells had lower glycolysis, TCA and protein synthesis activity than C cells. Total RNA was extracted from whole cells, isolated mitochondria and mitoplasts. The total number of miRNA detected by RT-qPCR in PNPT1 cells was about 6 times lower than in C cells: 47 vs 310 miRNAs but their average expression was higher (p<10-6). Their distribution among mitochondria, mitoplasts and cells was different (p<10-6): in C cells, there was a gradient from mitoplasts (153) to mitochondria (94) whereas in PNPT1 cells, there was no difference (130 vs 126).","PeriodicalId":266249,"journal":{"name":"Journal of World Mitochondria Society","volume":"22 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116747877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

MLQ protein regulates association of mitochondrially encoded subunits Fo-a and A6L with ATP synthase complex MLQ蛋白调节线粒体编码亚基Fo-a和A6L与ATP合成酶复合物的关联

Journal of World Mitochondria Society Pub Date : 2016-09-23 DOI: 10.18143/JWMS_v2i2_1983

K. Tauchmannová, P. Pecina, H. Nůsková, Dieu Hien Ho, J. Kovalčíková, T. Mráček, J. Houštěk

{"title":"MLQ protein regulates association of mitochondrially encoded subunits Fo-a and A6L with ATP synthase complex","authors":"K. Tauchmannová, P. Pecina, H. Nůsková, Dieu Hien Ho, J. Kovalčíková, T. Mráček, J. Houštěk","doi":"10.18143/JWMS_v2i2_1983","DOIUrl":"https://doi.org/10.18143/JWMS_v2i2_1983","url":null,"abstract":"The biogenesis of mammalian ATP synthase is complex process believed to proceed via several modules. The final phase is represented by incorporation of the two mtDNA-encoded subunits Fo-a and A6L, and probably of the two newly described accessory subunits DAPIT and MLQ. To confirm this, we followed the assembly state of ATP synthase in rho0 cells lacking both subunits Fo-a and A6L, cells harbouring 9205delTA microdeletion lacking subunit Fo-a, HEK293 cells with knockdown of DAPIT and HEK293 cells with knockout of MLQ. Absence of either Fo-a alone or Fo-a and A6L or MLQ results into the normal levels of labile, ~50 kDa smaller complex, which lacks all four subunits (Fo-a, A6L, DAPIT and MLQ). In all the cell lines tested we found that the total amount of individual subunits corresponds well with the amount of the subunit, associated with fully assembled ATP synthase complex. In the cells lacking MLQ the biosynthesis and assembly of both subunits Fo-a and A6L is preserved, but these subunits are fast degraded. We conclude that MLQ, Fo-a and A6L closely associate and their presence within the complex depends on each another. On the contrary, DAPIT protein seems to be incorporated at the very last step.","PeriodicalId":266249,"journal":{"name":"Journal of World Mitochondria Society","volume":"56 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115057884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Novel Functions of Lysine Demethylases as Mitochondrial Gatekeepers 赖氨酸去甲基酶作为线粒体看门人的新功能

Journal of World Mitochondria Society Pub Date : 2016-09-23 DOI: 10.18143/JWMS_V2I2_1974

Ling-Yu Wang, Hung‐Jung Wang, Chiu‐Lien Hung, Wen-Ching Wang, D. Ann, H. Kung

{"title":"Novel Functions of Lysine Demethylases as Mitochondrial Gatekeepers","authors":"Ling-Yu Wang, Hung‐Jung Wang, Chiu‐Lien Hung, Wen-Ching Wang, D. Ann, H. Kung","doi":"10.18143/JWMS_V2I2_1974","DOIUrl":"https://doi.org/10.18143/JWMS_V2I2_1974","url":null,"abstract":"There is considerable evidence that KDMs, lysine demethylases, are oncogenic drivers for cancers. We have focused on KDM4A (Wang et al., Cell Reports, 2016) and KDM8 (Wang et al., PNAS, 2014) in prostate carcinogenesis. Both KDM4A and KDM8 are overexpressed in prostate cancers and their overexpressions confer castration-resistance as well as therapy-resistance. KDM4A demethylates H3K9me3 and H3K36me2/3, whereas KDM8 demethylates H3K36me2 (Hsia et al., PNAS, 2010). They both are coactivators of AR and when overexpressed, activate androgen response genes. Here, we report that they have additional novel functions as the gate keepers of mitochondria. Pyruvate flow into mitochondria is important for TCA cycle and oxidative phosphorylation, which is regulated by two key kinases PKM2 (pyruvate kinase M2) and PDKs (pyruvate dehydrogenase kinases). Cytosolic PKM2, the predominant form in tumor cells, is responsible for the synthesis of pyruvate, the level of which dictates the flow to mitochondria or to lactate. PDK1 to 4 negatively regulate the conversion of pyruvate to acetyl-coA by phosphorylating pyruvate dehydrogenase. We have shown that KDM8 associates with PKM2 and effectively translocates PKM2 into the nucleus, where KDM8/PKM2 serve as coactivator of HIF-1a. The consequence of this translocation is the decrease of cytosolic PKM2 activity and the increase of the expression of glycolytic enzymes, resulting in the limited pyruvate flow into mitochondria. At the same time, it favors the anabolic pathways and the biosynthesis of macromolecules, required for metabolic adaptation of tumor cells. KDM4, as we reported recently, serves as an E2F1 coactivator enhances the expression of PDK1 and PDK3, which also limits the flow of pyruvate to acetyl-coA and oxidative phosphorylation. Thus, both KDM8 and KDM4A work in concert to deflect pyruvate from mitochondria in favor of tumor metabolism. The detailed mechanisms and their implications in cancer therapies will be discussed.","PeriodicalId":266249,"journal":{"name":"Journal of World Mitochondria Society","volume":"21 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129830983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A mithocondrial isoform of P300/CBP associated factor metabolically controls muscle differentiation P300/CBP相关因子的线粒体异构体代谢控制肌肉分化

Journal of World Mitochondria Society Pub Date : 2016-09-23 DOI: 10.18143/JWMS_V2I2_1977

M. Savoia

{"title":"A mithocondrial isoform of P300/CBP associated factor metabolically controls muscle differentiation","authors":"M. Savoia","doi":"10.18143/JWMS_V2I2_1977","DOIUrl":"https://doi.org/10.18143/JWMS_V2I2_1977","url":null,"abstract":"Histone acetyltransferases (HATs) catalyze the transfer from acetyl-CoA to conserved N-e-lysine residues of both histone and non-histone proteins modulating gene transcription and protein function. P300/CBP-associated factor (PCAF) is known to be involved in activation of the myogenic program, including the regulation of the transcription factor MyoD activity. Recently, it has been shown that the activity of mitochondrial enzymes can be affected by the lysine acetylation/deacetylation process. In C2C12 myoblasts, in fact, the inhibition of Sirtuin 3 (SIRT3) abrogated their terminal differentiation. So far, little is known about the role of HATs and, specifically, that of PCAF in mitochondria during muscle differentiation. Experimental evidence is provided in support of an unprecedented role of PCAF regulating mitochondrial function during skeletal muscle differentiation. Specifically, experiments show that PCAF constitutively localize into the mitochondria regulating lysine acetylation. In this context, co-immunoprecipitations indicated an association of PCAF with the isocitrate dehydrogenase 2 (IDH2) isoform with negative consequences on alpha-ketoglutarate (αKG) production. The depletion of a PCAF putative N-terminal mitochondrial localization sequence or its CRISPR/Cas9 inactivation decreased IDH2 acetylation impacting critically on muscle differentiation in the C2C12 cellular system. Our data suggest that PCAF may be relevant in the epi-metabolic regulation of muscle differentiation","PeriodicalId":266249,"journal":{"name":"Journal of World Mitochondria Society","volume":"27 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130592648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Increased plasma levels of circulating cell-free mitochondrial DNA in medication-free suicide attempters – associations with HPA-axis hyperactivity 无药物自杀企图者血浆循环无细胞线粒体DNA水平升高-与hpa轴过度活跃相关

Journal of World Mitochondria Society Pub Date : 2016-09-23 DOI: 10.18143/JWMS_V2I2_1981

D. Lindqvist, J. Fernström, C. Grudet, L. Ljunggren, L. Träskman-bendz, L. Ohlsson, Å. Westrin

{"title":"Increased plasma levels of circulating cell-free mitochondrial DNA in medication-free suicide attempters – associations with HPA-axis hyperactivity","authors":"D. Lindqvist, J. Fernström, C. Grudet, L. Ljunggren, L. Träskman-bendz, L. Ohlsson, Å. Westrin","doi":"10.18143/JWMS_V2I2_1981","DOIUrl":"https://doi.org/10.18143/JWMS_V2I2_1981","url":null,"abstract":"Data suggest that chronic stress may cause cellular damage and mitochondrial dysfunction[1-3], potentially leading to the release of mitochondrial DNA (mtDNA) into the bloodstream. Major Depressive Disorder has been associated with an increased amount of mtDNA in leukocytes from saliva samples and blood[4, 5], but no previous studies have measured plasma levels of free-circulating mtDNA in a clinical psychiatric sample. In this study, free circulating mtDNA was quantified in plasma samples from 37 suicide attempters, who had undergone a dexamethasone suppression test (DST), and 37 healthy controls. We hypothesized that free circulating mtDNA would be elevated in the suicide attempters and associated with HPA-axis hyperactivity. Suicide attempters had significantly higher plasma levels of free-circulating mtDNA compared to healthy controls at different time points (pre- and post-DST) (all p-values <2.98E-12, Cohen’s d ranging from 2.55-4.01). Pre-DST plasma levels of mtDNA were positively correlated with post-DST cortisol levels (rho=0.49, p<0.003). Suicide attempters may have elevated plasma levels of free-circulating mtDNA, which are related to impaired HPA-axis negative feedback. This peripheral index is consistent with increased cellular or mitochondrial damage. Future studies are needed to understand the relevance of increased free-circulating mtDNA in relation to the pathophysiology underlying suicidal behavior and depression.","PeriodicalId":266249,"journal":{"name":"Journal of World Mitochondria Society","volume":"16 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116872251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Integrated intra-mitochondria architecture of high-energy demand Drosophila IFM and its impact by mtDNA replication defect during aging 高能量需求果蝇IFM的线粒体内整合结构及其在衰老过程中mtDNA复制缺陷的影响

Journal of World Mitochondria Society Pub Date : 2016-09-23 DOI: 10.18143/JWMS_V2I2_1976

Chi-yu Fu

{"title":"Integrated intra-mitochondria architecture of high-energy demand Drosophila IFM and its impact by mtDNA replication defect during aging","authors":"Chi-yu Fu","doi":"10.18143/JWMS_V2I2_1976","DOIUrl":"https://doi.org/10.18143/JWMS_V2I2_1976","url":null,"abstract":"Mitochondria power the energy production that builds upon the architecture of double membranes and cristae invagination. This paper revealed a novel design of mitochondrial infrastructure to integrate the energetic state of the organelle. To meet high-energy demand, mitochondria of Drosophila muscle developed extensive intra-mitochondrial membrane switches between densely packed lamellar cristae that build spiral-like cristae network and bidirectional matrix confluency. The highly interconnected architecture allows rapid equilibration of membrane potential and biomolecules across integrated regions. Mutant flies with compromised mtDNA replication accumulated mitochondria containing subareas of swirling membrane besides normal cristae, which served as a morphological marker of defective mtDNA. We visualized, at the individual mitochondrial level, the structural and functional alterations of defective mtDNA that impaired local molecular composition and function, and affected fusion/fission dynamics. However, the subarea of normal cristae managed to maintain acceptable function that camouflaged defective mtDNA from quality control elimination.","PeriodicalId":266249,"journal":{"name":"Journal of World Mitochondria Society","volume":"8 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"121612355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Analysis of Mitochondrial Metabolism in situ: Combining Stable Isotope Labeling with Selective Permeabilization 线粒体原位代谢分析:结合稳定同位素标记和选择性渗透

Journal of World Mitochondria Society Pub Date : 2016-09-23 DOI: 10.18143/JWMS_v2i2_1982

Yannic Nonnenmacher

{"title":"Analysis of Mitochondrial Metabolism in situ: Combining Stable Isotope Labeling with Selective Permeabilization","authors":"Yannic Nonnenmacher","doi":"10.18143/JWMS_v2i2_1982","DOIUrl":"https://doi.org/10.18143/JWMS_v2i2_1982","url":null,"abstract":"Mitochondrial metabolism and its role in health and disease have emerged as a field of broad scientific interest in recent years. To date, it is well-established that mitochondrial dysfunction does not only play a vital role in cancer but also in other pathological conditions such as neurodegenerative diseases and inflammation. One important tool for the analysis of cellular metabolism is the application of stable isotope labeled substrates, which allow for the tracing of atoms throughout metabolic networks. While such analyses yield very detailed information about intracellular fluxes, the determination of compartment specific fluxes is far more challenging. Most approaches for the deconvolution of compartmented metabolism use computational models whereas experimental methods are rare. Here, we developed an experimental setup based on selective permeabilization of the cytosolic membrane that allows for the administration of stable isotope labeled substrates directly to mitochondria. In contrast to methods based on differential centrifugation, mitochondria are not removed from the cells but remain inside the permeabilized cell ghosts. We demonstrate how this approach can be used to infer metabolic changes in mitochondria induced by either chemical or genetic perturbations and give an outlook on its potential applications.","PeriodicalId":266249,"journal":{"name":"Journal of World Mitochondria Society","volume":"6 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130875824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Mitochondrial metabolism and thyroid hormones: a game of influence over adult neural stem cell fate decision? 线粒体代谢和甲状腺激素:对成体神经干细胞命运决定的影响?

Journal of World Mitochondria Society Pub Date : 2016-09-19 DOI: 10.18143/JWMS_V2I2_1963

J. Gothié, Anthony Sébillot, C. Luongo, M. Legendre, Marine Perret-Jeanneret, K. L. Blay, S. Remaud, B. Demeneix

{"title":"Mitochondrial metabolism and thyroid hormones: a game of influence over adult neural stem cell fate decision?","authors":"J. Gothié, Anthony Sébillot, C. Luongo, M. Legendre, Marine Perret-Jeanneret, K. L. Blay, S. Remaud, B. Demeneix","doi":"10.18143/JWMS_V2I2_1963","DOIUrl":"https://doi.org/10.18143/JWMS_V2I2_1963","url":null,"abstract":"Unlike differentiated cells, stem cells use aerobic glycosylation rather than oxidative phosphorylation1. Moreover, metabolic status influences stem cell determination2. Thyroid hormones (THs) regulate neural stem cell (NSC) commitment towards a neuronal phenotype in adult brain3, but also have major roles in mitochondrial metabolism4. Given these complimentary roles, we investigated the convergence of THs and mitochondrial metabolism on NSC fate determination towards neuronal or glial fate. Following stereotaxic injection of the mitochondrial membrane potential marker (JC-1) into the adult mouse lateral ventricle, we observed greater mitochondrial activity in cells committed toward a neuronal than an oligodendroglial phenotype. Further, in vitro studies in neurospheres using a dye revealing ROS production (hydroethidine) show that THs increase ROS production and promote neuronal determination. These studies also showed that the activated form of DRP1 (pDRP1S616), mediating mitochondrial fission, is preferentially detected in the cytosol of neuronal lineage cells. Together, these results show that both THs and mitochondrial activity impact NSCs fate decision. We hypothesize that THs govern NSCs commitment through their effects on mitochondria. Future work will address the impact of modulating DRP1 expression in different thyroid contexts. This work should provide new insights into the mechanisms governing adult NSCs fate.","PeriodicalId":266249,"journal":{"name":"Journal of World Mitochondria Society","volume":"73 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128147110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Modulation of Mitochondrial calcium uniporter complex in Ischemic Stroke 线粒体单转运钙复合物在缺血性卒中中的调节作用

Journal of World Mitochondria Society Pub Date : 2016-09-19 DOI: 10.18143/JWMS_V2I2_1956

K. Mallilankaraman, S. Baik, Sung-Chun Tang, T. Arumugam

{"title":"Modulation of Mitochondrial calcium uniporter complex in Ischemic Stroke","authors":"K. Mallilankaraman, S. Baik, Sung-Chun Tang, T. Arumugam","doi":"10.18143/JWMS_V2I2_1956","DOIUrl":"https://doi.org/10.18143/JWMS_V2I2_1956","url":null,"abstract":"Globally, Stroke ranks as the second leading cause of death. Reperfusion of the ischemic brain also initiates pathologic intracellular cascades that contribute to post-ischemic brain injury. Mitochondrial dysfunction has been known to be a major contributor of neuronal injury during stroke. During reperfusion, [Ca2+]m overload causes mitochondrial ROS overproduction, mitochondrial permeability transition, and activation of cell death signaling cascades. The consequences of mitochondrial calcium overload during stroke has been studied, but the causal upstream mechanisms that leads to calcium overload remains unclear. In the past five years, we1-4 and others have identified the molecular components of the mitochondrial calcium uniporter. The objective of the study was to investigate the expression pattern of uniporter complex during ischemic stroke. Using in-vitro (Oxygen-Glucose deprivation) and in-vivo (murine MCAO) model systems, we investigated in detail, the changes in expression pattern of uniporter components during Hypoxia-Reoxygenation and Ischemia-Reperfusion injury respectively. Finally, we validated our in-vitro and in-vivo findings in human stroke using stroke patient derived post-mortem brain samples. Collectively, data from our study suggests that the unique changes in expression of MCU complex, during reperfusion, results in enhanced [Ca2+]m uptake. The detailed findings of our study will be presented in the conference.","PeriodicalId":266249,"journal":{"name":"Journal of World Mitochondria Society","volume":"37 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125441396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0