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Mitochondrial supercomplexes

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https://www.readbyqxmd.com/read/27916530/enhanced-respiratory-chain-supercomplex-formation-in-response-to-exercise-in-human-skeletal-muscle
#1
Chiara Greggio, Pooja Jha, Sameer S Kulkarni, Sylviane Lagarrigue, Nicholas T Broskey, Marie Boutant, Xu Wang, Sonia Conde Alonso, Emmanuel Ofori, Johan Auwerx, Carles Cantó, Francesca Amati
Mitochondrial dysfunction is a hallmark of multiple metabolic complications. Physical activity is known to increase mitochondrial content in skeletal muscle, counteracting age-related decline in muscle function and protecting against metabolic and cardiovascular complications. Here, we investigated the effect of 4 months of exercise training on skeletal muscle mitochondria electron transport chain complexes and supercomplexes in 26 healthy, sedentary older adults. Exercise differentially modulated respiratory complexes...
November 28, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/27916505/cyclophilin-d-over-expression-increases-mitochondrial-complex-iii-activity-and-accelerates-supercomplex-formation
#2
Julie C Etzler, Mariana Bollo, Deborah Holstein, Janice Jianhong Deng, Viviana Perez, Da-Ting Lin, Arlan Richardson, Yidong Bai, James D Lechleiter
Cyclophilin D (CyPD), a mitochondrial matrix protein, has been widely studied for its role in mitochondrial-mediated cell death. Unexpectedly, we previously discovered that overexpression of CyPD in a stable cell line, increased mitochondrial membrane potentials and enhanced cell survival under conditions of oxidative stress. Here, we investigated the underlying mechanisms responsible for these findings. Spectrophotometric measurements in isolated mitochondria revealed that overexpression of CyPD in HEK293 cells increased respiratory chain activity, but only for Complex III (CIII)...
December 1, 2016: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/27912063/structure-of-mammalian-respiratory-supercomplex-i1iii2iv1
#3
Meng Wu, Jinke Gu, Runyu Guo, Yushen Huang, Maojun Yang
The mammalian respiratory chain complexes assemble into supercomplexes (SCs) and reside in the inner mitochondrial membrane to transfer electrons and establish the proton gradient for complex V to synthesize ATP. The precise arrangement of SCs is largely unknown. Here, we report a 4.0-Å cryo-electron microscopy (cryo-EM) structure of the major SC in porcine heart, the 1.7-MDa SCI1III2IV1. The complex III (CIII) dimer and complex IV (CIV) bind at the same side of the L-shaped complex I (CI). Several accessory or supernumerary subunits of CI, such as NDUFA11, NDUFB4, NDUFB8, and NDUFB9, directly contribute to the oligomerization of CI, CIII, and CIV...
December 1, 2016: Cell
https://www.readbyqxmd.com/read/27834740/being-right-on-q-shaping-eukaryotic-evolution
#4
REVIEW
Dave Speijer
Reactive oxygen species (ROS) formation by mitochondria is an incompletely understood eukaryotic process. I proposed a kinetic model [BioEssays (2011) 33: , 88-94] in which the ratio between electrons entering the respiratory chain via FADH2 or NADH (the F/N ratio) is a crucial determinant of ROS formation. During glucose breakdown, the ratio is low, while during fatty acid breakdown, the ratio is high (the longer the fatty acid, the higher is the ratio), leading to higher ROS levels. Thus, breakdown of (very-long-chain) fatty acids should occur without generating extra FADH2 in mitochondria...
November 15, 2016: Biochemical Journal
https://www.readbyqxmd.com/read/27830641/functional-asymmetry-and-electron-flow-in-the-bovine-respirasome
#5
Joana S Sousa, Deryck J Mills, Janet Vonck, Werner Kühlbrandt
Respirasomes are macromolecular assemblies of the respiratory chain complexes I, III and IV in the inner mitochondrial membrane. We determined the structure of supercomplex I1III2IV1 from bovine heart mitochondria by cryo-EM at 9 Å resolution. Most protein-protein contacts between complex I, III and IV in the membrane are mediated by supernumerary subunits. Of the two Rieske iron-sulfur cluster domains in the complex III dimer, one is resolved, indicating that this domain is immobile and unable to transfer electrons...
November 10, 2016: ELife
https://www.readbyqxmd.com/read/27828948/control-of-mitochondrial-function-and-cell-growth-by-the-atypical-cadherin-fat1
#6
Longyue L Cao, Dario F Riascos-Bernal, Prameladevi Chinnasamy, Charlene M Dunaway, Rong Hou, Mario A Pujato, Brian P O'Rourke, Veronika Miskolci, Liang Guo, Louis Hodgson, Andras Fiser, Nicholas E S Sibinga
Mitochondrial products such as ATP, reactive oxygen species, and aspartate are key regulators of cellular metabolism and growth. Abnormal mitochondrial function compromises integrated growth-related processes such as development and tissue repair, as well as homeostatic mechanisms that counteract ageing and neurodegeneration, cardiovascular disease, and cancer. Physiologic mechanisms that control mitochondrial activity in such settings remain incompletely understood. Here we show that the atypical Fat1 cadherin acts as a molecular 'brake' on mitochondrial respiration that regulates vascular smooth muscle cell (SMC) proliferation after arterial injury...
November 9, 2016: Nature
https://www.readbyqxmd.com/read/27799543/complex-i-assembly-into-supercomplexes-determines-differential-mitochondrial-ros-production-in-neurons-and-astrocytes
#7
Irene Lopez-Fabuel, Juliette Le Douce, Angela Logan, Andrew M James, Gilles Bonvento, Michael P Murphy, Angeles Almeida, Juan P Bolaños
Neurons depend on oxidative phosphorylation for energy generation, whereas astrocytes do not, a distinctive feature that is essential for neurotransmission and neuronal survival. However, any link between these metabolic differences and the structural organization of the mitochondrial respiratory chain is unknown. Here, we investigated this issue and found that, in neurons, mitochondrial complex I is predominantly assembled into supercomplexes, whereas in astrocytes the abundance of free complex I is higher...
November 15, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27794519/a-novel-fission-independent-role-of-dynamin-related-protein-1-in-cardiac-mitochondrial-respiration
#8
Huiliang Zhang, Pei Wang, Sara Bisetto, Yisang Yoon, Quan Chen, Shey-Shing Sheu, Wang Wang
AIMS: Mitochondria in adult cardiomyocytes exhibit static morphology and infrequent dynamic changes, despite the high abundance of fission and fusion regulatory proteins in the heart. Previous reports have indicated that fusion proteins may bear functions beyond morphology regulation. Here, we investigated the role of fission protein, dynamin-related protein 1 (DRP1), on mitochondrial respiration regulation in adult cardiomyocytes. METHODS AND RESULTS: By using genetic or pharmacological approaches, we manipulated the activity or protein level of fission and fusion proteins and found they mildly influenced mitochondrial morphology in adult rodent cardiomyocytes, which is in contrast to their significant effect in H9C2 cardiac myoblasts...
October 29, 2016: Cardiovascular Research
https://www.readbyqxmd.com/read/27783852/mitochondrial-actions-of-thyroid-hormone
#9
Antonia Lanni, Maria Moreno, Fernando Goglia
The hypermetabolic effects of thyroid hormones (THs), the major endocrine regulators of metabolic rate, are widely recognized. Although, the cellular mechanisms underlying these effects have been extensively investigated, much has yet to be learned about how TH regulates diverse cellular functions. THs have a profound impact on mitochondria, the organelles responsible for the majority of cellular energy production, and several studies have been devoted to understand the respective importance of the nuclear and mitochondrial pathways for organelle activity...
September 15, 2016: Comprehensive Physiology
https://www.readbyqxmd.com/read/27720676/the-assembly-pathway-of-mitochondrial-respiratory-chain-complex-i
#10
Sergio Guerrero-Castillo, Fabian Baertling, Daniel Kownatzki, Hans J Wessels, Susanne Arnold, Ulrich Brandt, Leo Nijtmans
Mitochondrial complex I is the largest integral membrane enzyme of the respiratory chain and consists of 44 different subunits encoded in the mitochondrial and nuclear genome. Its biosynthesis is a highly complicated and multifaceted process involving at least 14 additional assembly factors. How these subunits assemble into a functional complex I and where the assembly factors come into play is largely unknown. Here, we applied a dynamic complexome profiling approach to elucidate the assembly of human mitochondrial complex I and its further incorporation into respiratory chain supercomplexes...
September 30, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/27694445/stard7-protein-deficiency-adversely-affects-the-phosphatidylcholine-composition-respiratory-activity-and-cristae-structure-of-mitochondria
#11
Yasuhiro Horibata, Hiromi Ando, Peixiang Zhang, Laurent Vergnes, Chieko Aoyama, Masahiko Itoh, Karen Reue, Hiroyuki Sugimoto
Phosphatidylcholine (PC) is a major phospholipid of mitochondria, comprising 40-50% of both the outer and the inner membranes. However, PC must be imported from its production organelles because mitochondria lack the enzymes essential for PC biosynthesis. In a previous study, we found that StarD7 mediates the intracellular transfer of PC to mitochondria. Therefore, in this study, we analyzed the contribution of StarD7 to the maintenance of mitochondrial phospholipid content and function using siRNA-mediated knockdown and knock-out (KO) of the StarD7 gene in HEPA-1 cells...
November 25, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27662906/overlapping-role-of-respiratory-supercomplex-factor-rcf2-and-its-n-terminal-homolog-rcf3-in-saccharomyces-cerevisiae
#12
Katharina Römpler, Tobias Müller, Lisa Juris, Mirjam Wissel, Milena Vukotic, Kay Hofmann, Markus Deckers
The mitochondrial electron transport chain consists of individual protein complexes arranged into large macromolecular structures, termed respiratory chain supercomplexes or respirasomes. In the yeast Saccharomyces cerevisiae, respiratory chain supercomplexes form by association of the bc1 complex with the cytochrome c oxidase. Formation and maintenance of these assemblies are promoted by specific respiratory supercomplex factors, the Rcf proteins. For these proteins a regulatory function in bridging the electron transfer within supercomplexes has been proposed...
November 4, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27626371/accessory-subunits-are-integral-for-assembly-and-function-of-human-mitochondrial-complex-i
#13
David A Stroud, Elliot E Surgenor, Luke E Formosa, Boris Reljic, Ann E Frazier, Marris G Dibley, Laura D Osellame, Tegan Stait, Traude H Beilharz, David R Thorburn, Agus Salim, Michael T Ryan
Complex I (NADH:ubiquinone oxidoreductase) is the first enzyme of the mitochondrial respiratory chain and is composed of 45 subunits in humans, making it one of the largest known multi-subunit membrane protein complexes. Complex I exists in supercomplex forms with respiratory chain complexes III and IV, which are together required for the generation of a transmembrane proton gradient used for the synthesis of ATP. Complex I is also a major source of damaging reactive oxygen species and its dysfunction is associated with mitochondrial disease, Parkinson's disease and ageing...
September 14, 2016: Nature
https://www.readbyqxmd.com/read/27620332/isolation-of-yeast-complex-iv-in-native-lipid-nanodiscs
#14
Irina A Smirnova, Dan Sjöstrand, Fei Li, Markus Björck, Jacob Schäfer, Henrik Östbye, Martin Högbom, Christoph von Ballmoos, Gabriel C Lander, Pia Ädelroth, Peter Brzezinski
We used the amphipathic styrene maleic acid (SMA) co-polymer to extract cytochrome c oxidase (CytcO) in its native lipid environment from S. cerevisiae mitochondria. Native nanodiscs containing one CytcO per disc were purified using affinity chromatography. The longest cross-sections of the native nanodiscs were 11nm×14nm. Based on this size we estimated that each CytcO was surrounded by ~100 phospholipids. The native nanodiscs contained the same major phospholipids as those found in the mitochondrial inner membrane...
December 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27604998/elucidating-mitochondrial-electron-transport-chain-supercomplexes-in-the-heart-during-ischemia-reperfusion
#15
Sehwan Jang, Taber S Lewis, Corey Powers, Zaza Khuchua, Christopher P Baines, Peter Wipf, Sabzali Javadov
AIMS: Mitochondrial supercomplexes (SCs) are the large supramolecular assembly of individual electron transport chain (ETC) complexes that apparently provide highly efficient ATP synthesis and reduce electron leakage and reactive oxygen species (ROS) production. Oxidative stress during cardiac ischemia-reperfusion (IR) can result in degradation of SCs through oxidation of cardiolipin (CL). Also, IR induces calcium overload and enhances reactive oxygen species (mitROS) in mitochondria that result in the opening of the nonselective permeability transition pores (PTP)...
November 11, 2016: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/27550821/cox7ar-is-a-stress-inducible-mitochondrial-cox-subunit-that-promotes-breast-cancer-malignancy
#16
Kezhong Zhang, Guohui Wang, Xuebao Zhang, Philipp P Hüttemann, Yining Qiu, Jenney Liu, Allison Mitchell, Icksoo Lee, Chao Zhang, Jin-Sook Lee, Petr Pecina, Guojun Wu, Zeng-Quan Yang, Maik Hüttemann, Lawrence I Grossman
Cytochrome c oxidase (COX), the terminal enzyme of the mitochondrial respiratory chain, plays a key role in regulating mitochondrial energy production and cell survival. COX subunit VIIa polypeptide 2-like protein (COX7AR) is a novel COX subunit that was recently found to be involved in mitochondrial supercomplex assembly and mitochondrial respiration activity. Here, we report that COX7AR is expressed in high energy-demanding tissues, such as brain, heart, liver, and aggressive forms of human breast cancer cells...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27545886/cox7a2l-is-a-mitochondrial-complex-iii-binding-protein-that-stabilizes-the-iii2-iv-supercomplex-without-affecting-respirasome-formation
#17
Rafael Pérez-Pérez, Teresa Lobo-Jarne, Dusanka Milenkovic, Arnaud Mourier, Ana Bratic, Alberto García-Bartolomé, Erika Fernández-Vizarra, Susana Cadenas, Aitor Delmiro, Inés García-Consuegra, Joaquín Arenas, Miguel A Martín, Nils-Göran Larsson, Cristina Ugalde
Mitochondrial respiratory chain (MRC) complexes I, III, and IV associate into a variety of supramolecular structures known as supercomplexes and respirasomes. While COX7A2L was originally described as a supercomplex-specific factor responsible for the dynamic association of complex IV into these structures to adapt MRC function to metabolic variations, this role has been disputed. Here, we further examine the functional significance of COX7A2L in the structural organization of the mammalian respiratory chain...
August 30, 2016: Cell Reports
https://www.readbyqxmd.com/read/27506242/d-lactate-dehydrogenase-links-methylglyoxal-degradation-and-electron-transport-through-cytochrome-c
#18
Elina Welchen, Jessica Schmitz, Philippe Fuchs, Lucila García, Stephan Wagner, Judith Wienstroer, Peter Schertl, Hans-Peter Braun, Markus Schwarzländer, Daniel H Gonzalez, Veronica G Maurino
Glycolysis generates methylglyoxal (MGO) as an unavoidable, cytotoxic by-product in plant cells. MGO scavenging is performed by the glyoxalase system, which produces d-lactate as an end product. d-Lactate dehydrogenase (d-LDH) is encoded by a single gene in Arabidopsis (Arabidopsis thaliana; At5g06580). It catalyzes in vitro the oxidation of d-lactate to pyruvate using flavin adenine dinucleotide as a cofactor; knowledge of its function in the context of the plant cell remains sketchy. Blue native-polyacrylamide gel electrophoresis of mitochondrial extracts combined with in gel activity assays using different substrates and tandem mass spectrometry allowed us to definitely show that d-LDH acts specifically on d-lactate, is active as a dimer, and does not associate with respiratory supercomplexes of the inner mitochondrial membrane...
October 2016: Plant Physiology
https://www.readbyqxmd.com/read/27503613/cardiolipin-deficiency-causes-a-dissociation-of-the-b-6-c-caa-3-megacomplex-in-b-subtilis-membranes
#19
Led Yered Jafet García Montes de Oca, Tecilli Cabellos Avelar, Gerardo Ignacio Picón Garrido, Alicia Chagoya-López, Luis González de la Vara, Norma Laura Delgado Buenrostro, Yolanda Irasema Chirino-López, Carlos Gómez-Lojero, Emma Berta Gutiérrez-Cirlos
The associations among respiratory complexes in energy-transducing membranes have been established. In fact, it is known that the Gram-negative bacteria Paracoccus denitrificans and Escherichia coli have respiratory supercomplexes in their membranes. These supercomplexes are important for channeling substrates between enzymes in a metabolic pathway, and the assembly of these supercomplexes depends on the protein subunits and membrane lipids, mainly cardiolipin, which is present in both the mitochondrial inner membrane and bacterial membranes...
August 2016: Journal of Bioenergetics and Biomembranes
https://www.readbyqxmd.com/read/27495222/impaired-cardiolipin-biosynthesis-prevents-hepatic-steatosis-and-diet-induced-obesity
#20
Laura K Cole, Edgar M Meija, Marilyne Vandel, Genevieve C Sparagna, Steven M Claypool, Laura Dyck-Chan, Julianne Klein, Grant M Hatch
Mitochondria are the nexus of energy metabolism and consequently their dysfunction has been implicated in the development of metabolic complications and the progression to insulin resistance and type II diabetes. The unique tetra-acyl phospholipid cardiolipin (CL) is located in the inner mitochondrial membrane where it maintains mitochondrial integrity. Here we show that knock-down of Tafazzin (TAZ kd), a CL transacylase, in mice results in protection against the development of obesity, insulin resistance and hepatic steatosis...
August 5, 2016: Diabetes
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