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Mitochondrial supercomplexes

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https://www.readbyqxmd.com/read/28719865/antioxidant-effect-of-exercise-exploring-the-role-of-the-mitochondrial-complex-i-superassembly
#1
J R Huertas, S Al Fazazi, A Hidalgo-Gutierrez, L C López, R A Casuso
Mitochondrial respiratory complexes become assembled into supercomplexes (SC) under physiological conditions. One of the functional roles of these entities is the limitation of reactive oxygen species (ROS) produced by complex I (CI) of the respiratory chain. We sought to determine whether the systemic antioxidant effect of exercise is mediated by the assembly of mitochondrial CIs into SCs in rats. Male Wistar rats were exercise trained or remained sedentary for ten weeks; then, blood samples were collected, and the gastrocnemius muscle was isolated...
July 11, 2017: Redox Biology
https://www.readbyqxmd.com/read/28658629/definition-of-a-high-confidence-mitochondrial-proteome-at-quantitative-scale
#2
Marcel Morgenstern, Sebastian B Stiller, Philipp Lübbert, Christian D Peikert, Stefan Dannenmaier, Friedel Drepper, Uri Weill, Philipp Höß, Reinhild Feuerstein, Michael Gebert, Maria Bohnert, Martin van der Laan, Maya Schuldiner, Conny Schütze, Silke Oeljeklaus, Nikolaus Pfanner, Nils Wiedemann, Bettina Warscheid
Mitochondria perform central functions in cellular bioenergetics, metabolism, and signaling, and their dysfunction has been linked to numerous diseases. The available studies cover only part of the mitochondrial proteome, and a separation of core mitochondrial proteins from associated fractions has not been achieved. We developed an integrative experimental approach to define the proteome of yeast mitochondria. We classified > 3,300 proteins of mitochondria and mitochondria-associated fractions and defined 901 high-confidence mitochondrial proteins, expanding the set of mitochondrial proteins by 82...
June 27, 2017: Cell Reports
https://www.readbyqxmd.com/read/28654702/stomatin-like-protein-2-deficiency-results-in-impaired-mitochondrial-translation
#3
Panagiotis Mitsopoulos, Orsolya Lapohos, Woranontee Weraarpachai, Hana Antonicka, Yu-Han Chang, Joaquín Madrenas
Mitochondria translate the RNAs for 13 core polypeptides of respiratory chain and ATP synthase complexes that are essential for the assembly and function of these complexes. This process occurs in close proximity to the mitochondrial inner membrane. However, the mechanisms and molecular machinery involved in mitochondrial translation are not fully understood, and defects in this process can result in severe diseases. Stomatin-like protein (SLP)-2 is a mainly mitochondrial protein that forms cardiolipin- and prohibitin-enriched microdomains in the mitochondrial inner membrane that are important for the formation of respiratory supercomplexes and their function...
2017: PloS One
https://www.readbyqxmd.com/read/28637784/tnfr2-stimulation-promotes-mitochondrial-fusion-via-stat3-and-nf-kb-dependent-activation-of-opa1-expression
#4
Jinliang Nan, Hengxun Hu, Yong Sun, Lianlian Zhu, Yingchao Wang, Zhiwei Zhong, Jing Zhao, Na Zhang, Ya Wang, Yaping Wang, Jian Ye, Ling Zhang, Xinyang Hu, Wei Zhu, Jian'an Wang
Rationale: Mitochondria are important cellular organelles and play essential roles in maintaining cell structure and function. Emerging evidence indicates that in addition to having pro-inflammatory and pro-apoptotic effects, tumor necrosis factor α (TNFα) can, under certain circumstances, promote improvements in mitochondrial integrity and function, phenomena that can be ascribed to the existence of TNFα receptor 2 (TNFR2). Objective: The present study aimed to investigate whether and how TNFR2 activation mediates the effects of TNFα on mitochondria...
June 21, 2017: Circulation Research
https://www.readbyqxmd.com/read/28630166/deficiency-of-phb-complex-impairs-respiratory-supercomplex-formation-and-activates-mitochondrial-flashes
#5
Chongshu Jian, Fengli Xu, Tingting Hou, Tao Sun, Li Jinghang, Heping Cheng, Xianhua Wang
Prohibitins (prohibitin 1, PHB1, and prohibitin 2, PHB2) are evolutionally conserved and ubiquitously expressed mitochondrial protein. PHBs form multimeric ring complexes acting as scaffolds in the inner mitochondrial membrane. Mitochondrial flashes (mitoflashes) are newly discovered mitochondrial signaling events which reflect electrical and chemical excitations of the organelle. Here we investigate possible roles of PHBs in the regulation of mitoflash signaling. Down-regulation of PHBs increases mitoflash frequency by up to 5...
June 19, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28605384/analyzing-supercomplexes-of-the-mitochondrial-electron-transport-chain-with-native-electrophoresis-in-gel-assays-and-electroelution
#6
Gisela Beutner, George Arthur Porter
The mitochondrial electron transport chain (ETC) transduces the energy derived from the breakdown of various fuels into the bioenergetic currency of the cell, ATP. The ETC is composed of 5 massive protein complexes, which also assemble into supercomplexes called respirasomes (C-I, C-III, and C-IV) and synthasomes (C-V) that increase the efficiency of electron transport and ATP production. Various methods have been used for over 50 years to measure ETC function, but these protocols do not provide information on the assembly of individual complexes and supercomplexes...
June 1, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28593021/tissue-and-condition-specific-isoforms-of-mammalian-cytochrome-c-oxidase-subunits-from-function-to-human-disease
#7
REVIEW
Christopher A Sinkler, Hasini Kalpage, Joseph Shay, Icksoo Lee, Moh H Malek, Lawrence I Grossman, Maik Hüttemann
Cytochrome c oxidase (COX) is the terminal enzyme of the electron transport chain and catalyzes the transfer of electrons from cytochrome c to oxygen. COX consists of 14 subunits, three and eleven encoded, respectively, by the mitochondrial and nuclear DNA. Tissue- and condition-specific isoforms have only been reported for COX but not for the other oxidative phosphorylation complexes, suggesting a fundamental requirement to fine-tune and regulate the essentially irreversible reaction catalyzed by COX. This article briefly discusses the assembly of COX in mammals and then reviews the functions of the six nuclear-encoded COX subunits that are expressed as isoforms in specialized tissues including those of the liver, heart and skeletal muscle, lung, and testes: COX IV-1, COX IV-2, NDUFA4, NDUFA4L2, COX VIaL, COX VIaH, COX VIb-1, COX VIb-2, COX VIIaH, COX VIIaL, COX VIIaR, COX VIIIH/L, and COX VIII-3...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28584055/prolonged-fasting-suppresses-mitochondrial-nlrp3-inflammasome-assembly-and-activation-via-sirt3-mediated-activation-of-superoxide-dismutase-2
#8
Javier Traba, Sarah S Geiger, Miriam Kwarteng Siaw, Kim Han, One Hyuk Ra, Richard M Siegel, David Gius, Michael N Sack
Twenty-four hours of fasting is known to blunt activation of the human NLRP3 inflammasome. This effect might be mediated by SIRT3 activation, controlling mitochondrial reactive oxygen species (ROS). To characterize the molecular underpinnings of this fasting effect, we comparatively analyzed the NLRP3 inflammasome response to nutrient deprivation in wildtype and SIRT3-knockout mice. Consistent with previous findings for human NLRP3, prolonged fasting blunted the inflammasome in wildtype mice but not in SIRT3-knockout mice...
June 5, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28582861/post-translational-oxidative-modifications-of-mitochondrial-complex-i-nadh-ubiquinone-oxidoreductase-implications-for-pathogenesis-and-therapeutics-in-human-diseases
#9
M M Srinivas Bharath
Mitochondrial complex I (NADH: ubiquinone oxidoreductase; CI) is central to the electron transfer chain (ETC), oxidative phosphorylation, and ATP production in eukaryotes. CI is a multi-subunit complex with a complicated yet organized structure that optimally connects electron transfer with proton translocation and forms higher-order supercomplexes with other ETC complexes. Efforts to understand the molecular genetics, expression profile of subunits, and structure-function relationship of CI have increased over the years due to the direct role of the complex in human diseases...
May 30, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28579242/mitochonic-acid-5-ma-5-facilitates-atp-synthase-oligomerization-and-cell-survival-in-various-mitochondrial-diseases
#10
Tetsuro Matsuhashi, Takeya Sato, Shin-Ichiro Kanno, Takehiro Suzuki, Akihiro Matsuo, Yuki Oba, Motoi Kikusato, Emi Ogasawara, Tai Kudo, Kosuke Suzuki, Osamu Ohara, Hiroko Shimbo, Fumika Nanto, Hiroaki Yamaguchi, Daisuke Saigusa, Yasuno Mukaiyama, Akiko Watabe, Koichi Kikuchi, Hisato Shima, Eikan Mishima, Yasutoshi Akiyama, Yoshitsugu Oikawa, H O Hsin-Jung, Yukako Akiyama, Chitose Suzuki, Mitsugu Uematsu, Masaki Ogata, Naonori Kumagai, Masaaki Toyomizu, Atsushi Hozawa, Nariyasu Mano, Yuji Owada, Setsuya Aiba, Teruyuki Yanagisawa, Yoshihisa Tomioka, Shigeo Kure, Sadayoshi Ito, Kazuto Nakada, Ken-Ichiro Hayashi, Hitoshi Osaka, Takaaki Abe
Mitochondrial dysfunction increases oxidative stress and depletes ATP in a variety of disorders. Several antioxidant therapies and drugs affecting mitochondrial biogenesis are undergoing investigation, although not all of them have demonstrated favorable effects in the clinic. We recently reported a therapeutic mitochondrial drug mitochonic acid MA-5 (Tohoku J. Exp. Med., 2015). MA-5 increased ATP, rescued mitochondrial disease fibroblasts and prolonged the life span of the disease model "Mitomouse" (JASN, 2016)...
June 2017: EBioMedicine
https://www.readbyqxmd.com/read/28533780/innate-immune-function-of-mitochondrial-metabolism
#11
REVIEW
David Sancho, Michel Enamorado, Johan Garaude
Sensing of microbe-associated molecular patterns or danger signals by innate immune receptors drives a complex exchange of information. Innate receptor signaling not only triggers transcriptional events but also induces profound changes in metabolic fluxes, redox balance, and metabolite abundance thereby influencing immune cell function. Mitochondria are at the core of metabolic adaptation to the changing environment. The close interaction between mitochondrial metabolism and immune signaling has emerged as a central regulator of innate sensing...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28490636/the-cox1-c-terminal-domain-is-a-central-regulator-of-cytochrome-c-oxidase-biogenesis-in-yeast-mitochondria
#12
Rodolfo García-Villegas, Yolanda Camacho-Villasana, Miguel Ángel Shingú-Vázquez, Alfredo Cabrera-Orefice, Salvador Uribe-Carvajal, Thomas D Fox, Xochitl Pérez-Martínez
Cytochrome c oxidase (CcO) is the last electron acceptor in the respiratory chain. The CcO core is formed by mitochondrial DNA-encoded Cox1, Cox2, and Cox3 subunits. Cox1 synthesis is highly regulated; for example, if CcO assembly is blocked, Cox1 synthesis decreases. Mss51 activates translation of COX1 mRNA and interacts with Cox1 protein in high-molecular-weight complexes (COA complexes) to form the Cox1 intermediary assembly module. Thus, Mss51 coordinates both Cox1 synthesis and assembly. We previously reported that the last 15 residues of the Cox1 C terminus regulate Cox1 synthesis by modulating an interaction of Mss51 with Cox14, another component of the COA complexes...
June 30, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28437736/murine-diet-induced-obesity-remodels-cardiac-and-liver-mitochondrial-phospholipid-acyl-chains-with-differential-effects-on-respiratory-enzyme-activity
#13
E Madison Sullivan, Amy Fix, Miranda J Crouch, Genevieve C Sparagna, Tonya N Zeczycki, David A Brown, Saame Raza Shaikh
Cardiac phospholipids, notably cardiolipin, undergo acyl chain remodeling and/or loss of content in aging and cardiovascular diseases, which is postulated to mechanistically impair mitochondrial function. Less is known about how diet-induced obesity influences cardiac phospholipid acyl chain composition and thus mitochondrial responses. Here we first tested if a high fat diet remodeled murine cardiac mitochondrial phospholipid acyl chain composition and consequently disrupted membrane packing, supercomplex formation and respiratory enzyme activity...
July 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28408307/mitochondrial-respiratory-chain-disorganization-in-parkinson-s-disease-relevant-pink1-and-dj1-mutants
#14
Irene Lopez-Fabuel, Lucia Martin-Martin, Monica Resch-Beusher, Garikoitz Azkona, Rosario Sanchez-Pernaute, Juan P Bolaños
Brain mitochondrial complex I (CI) damage is associated with the loss of the dopaminergic neurons of the Substantia Nigra in Parkinson's Disease (PD) patients. However, whether CI inhibition is associated with any alteration of the mitochondrial respiratory chain (MRC) organization in PD patients is unknown. To address this issue, here we analyzed the MRC by blue native gel electrophoresis (BNGE) followed by western blotting, in mitochondria purified from fibroblasts of patients harboring PD-relevant Pink1 mutations...
April 10, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28404750/human-adenine-nucleotide-translocases-physically-and-functionally-interact-with-respirasomes
#15
Ya-Wen Lu, Michelle Grace Acoba, Kandasamy Selvaraju, Tai-Chung Huang, Raja S Nirujogi, Gajanan Sathe, Akhilesh Pandey, Steven M Claypool
Members of the adenine nucleotide translocase (ANT) family exchange ADP for ATP across the mitochondrial inner membrane, an activity that is essential for oxidative phosphorylation (OXPHOS). Mutations in or dysregulation of ANTs is associated with progressive external ophthalmoplegia, cardiomyopathy, nonsyndromic intellectual disability, apoptosis, and the Warburg effect. Binding partners of human ANTs have not been systematically identified. The absence of such information has prevented a detailed molecular understanding of the assorted ANT-associated diseases, including insight into their disparate phenotypic manifestations...
June 1, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28228763/cardiolipin-supports-respiratory-enzymes-in-plants-in-different-ways
#16
Jakob Petereit, Kenta Katayama, Christin Lorenz, Linda Ewert, Peter Schertl, Andreas Kitsche, Hajime Wada, Margrit Frentzen, Hans-Peter Braun, Holger Eubel
In eukaryotes the presence of the dimeric phospholipid cardiolipin (CL) is limited to the mitochondrial membranes. It resides predominantly in the inner membrane where it interacts with components of the mitochondrial electron transfer chain. CL deficiency has previously been shown to affect abundances of the plant NADH-dehydrogenase complex and its association with dimeric cyctochrome c reductase. Using an Arabidopsis thaliana knock-out mutant for the final enzyme of CL biosynthesis we here extend current knowledge on the dependence of plant respiration on CL...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28197854/mitochondrial-complex-i-activity-is-conditioned-by-supercomplex-i-iii2-iv-assembly-in-brain-cells-relevance-for-parkinson-s-disease
#17
Irene Lopez-Fabuel, Monica Resch-Beusher, Monica Carabias-Carrasco, Angeles Almeida, Juan P Bolaños
The assembly of complex I (CI) with complexes III (CIII) and IV (CIV) of the mitochondrial respiratory chain (MRC) to configure I-III- or I-III-IV-containing supercomplexes (SCs) regulates mitochondrial energy efficiency and reactive oxygen species (mROS) production. However, whether the occurrence of SCs impacts on CI specific activity remains unknown to our knowledge. To investigate this issue, here we determined CI activity in primary neurons and astrocytes, cultured under identical antioxidants-free medium, from two mouse strains (C57Bl/6 and CBA) and Wistar rat, i...
February 14, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28174208/l-opa1-regulates-mitoflash-biogenesis-independently-from-membrane-fusion
#18
Manon Rosselin, Jaime Santo-Domingo, Flavien Bermont, Marta Giacomello, Nicolas Demaurex
Mitochondrial flashes mediated by optic atrophy 1 (OPA1) fusion protein are bioenergetic responses to stochastic drops in mitochondrial membrane potential (Δψm) whose origin is unclear. Using structurally distinct genetically encoded pH-sensitive probes, we confirm that flashes are matrix alkalinization transients, thereby establishing the pH nature of these events, which we renamed "mitopHlashes". Probes located in cristae or intermembrane space as verified by electron microscopy do not report pH changes during Δψm drops or respiratory chain inhibition...
March 2017: EMBO Reports
https://www.readbyqxmd.com/read/28167530/mutational-analysis-of-the-qrrq-motif-in-the-yeast-hig1-type-2-protein-rcf1-reveals-a-regulatory-role-for-the-cytochrome-c-oxidase-complex
#19
Joshua Garlich, Valentina Strecker, Ilka Wittig, Rosemary A Stuart
The yeast Rcf1 protein is a member of the conserved family of proteins termed the hypoxia-induced gene (domain) 1 (Hig1 or HIGD1) family. Rcf1 interacts with components of the mitochondrial oxidative phosphorylation system, in particular the cytochrome bc1 (complex III)-cytochrome c oxidase (complex IV) supercomplex (termed III-IV) and the ADP/ATP carrier proteins. Rcf1 plays a role in the assembly and modulation of the activity of complex IV; however, the molecular basis for how Rcf1 influences the activity of complex IV is currently unknown...
March 31, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28130547/mitochondrial-protein-interactome-elucidated-by-chemical-cross-linking-mass-spectrometry
#20
Devin K Schweppe, Juan D Chavez, Chi Fung Lee, Arianne Caudal, Shane E Kruse, Rudy Stuppard, David J Marcinek, Gerald S Shadel, Rong Tian, James E Bruce
Mitochondrial protein interactions and complexes facilitate mitochondrial function. These complexes range from simple dimers to the respirasome supercomplex consisting of oxidative phosphorylation complexes I, III, and IV. To improve understanding of mitochondrial function, we used chemical cross-linking mass spectrometry to identify 2,427 cross-linked peptide pairs from 327 mitochondrial proteins in whole, respiring murine mitochondria. In situ interactions were observed in proteins throughout the electron transport chain membrane complexes, ATP synthase, and the mitochondrial contact site and cristae organizing system (MICOS) complex...
February 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
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