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Mitochondrial supercomplexes

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https://www.readbyqxmd.com/read/28533780/innate-immune-function-of-mitochondrial-metabolism
#1
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-carboxyl-terminal-domain-is-a-central-regulator-of-cytochrome-c-oxidase-biogenesis-in-yeast-mitochondria
#2
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...
May 10, 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
#3
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...
April 12, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28408307/mitochondrial-respiratory-chain-disorganization-in-parkinson-s-disease-relevant-pink1-and-dj1-mutants
#4
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
#5
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, non-syndromic 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...
April 12, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28228763/cardiolipin-supports-respiratory-enzymes-in-plants-in-different-ways
#6
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
#7
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
#8
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
#9
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
#10
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
https://www.readbyqxmd.com/read/28107462/cytochrome-c-oxidase-biogenesis-and-metallochaperone-interactions-steps-in-the-assembly-pathway-of-a-bacterial-complex
#11
Sonja Schimo, Ilka Wittig, Klaas M Pos, Bernd Ludwig
Biogenesis of mitochondrial cytochrome c oxidase (COX) is a complex process involving the coordinate expression and assembly of numerous subunits (SU) of dual genetic origin. Moreover, several auxiliary factors are required to recruit and insert the redox-active metal compounds, which in most cases are buried in their protein scaffold deep inside the membrane. Here we used a combination of gel electrophoresis and pull-down assay techniques in conjunction with immunostaining as well as complexome profiling to identify and analyze the composition of assembly intermediates in solubilized membranes of the bacterium Paracoccus denitrificans...
2017: PloS One
https://www.readbyqxmd.com/read/28007968/nitrite-protects-mitochondrial-structure-and-function-under-hypoxia
#12
Kapuganti Jagadis Gupta, Chun Pong Lee, R George Ratcliffe
Oxygen deprivation leads to changes in mitochondrial morphology and impaired flow of reducing equivalents through the electron transport chain. The extent of these changes depends on the duration and severity of the treatment as well as on the species and cell type. Nitrate is known to ameliorate these effects in some instances, but it is possible that it is nitrite, rather than nitrate, that is the key to the mechanism. To test this, mitochondria were isolated from 21-day-old pea (Pisum sativum) roots and incubated for 90 min under normoxia or hypoxia in the presence or absence of 0...
October 25, 2016: Plant & Cell Physiology
https://www.readbyqxmd.com/read/27997587/cox7a2l-scafi-and-pre-complex-iii-modify-respiratory-chain-supercomplex-formation-in-different-mouse-strains-with-a-bcs1l-mutation
#13
Mina Davoudi, Heike Kotarsky, Eva Hansson, Jukka Kallijärvi, Vineta Fellman
The COX7A2L (Supercomplex Assembly Factor I, SCAFI) protein has been proposed to be a mitochondrial supercomplex assembly factor required for respirasome (supercomplex containing complexes I, III, and IV) formation. In the C57BL/6 mouse strain a homozygous in-frame 6-base-pair deletion in the COX7a2l/SCAF1 gene resulting in unstable protein and suggesting loss of function was previously identified. The loss of SCAFI was shown to impede respirasome formation, a major concern for the use of C57BL mouse strains in mitochondrial research...
2016: PloS One
https://www.readbyqxmd.com/read/27916530/enhanced-respiratory-chain-supercomplex-formation-in-response-to-exercise-in-human-skeletal-muscle
#14
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...
February 7, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/27916505/cyclophilin-d-over-expression-increases-mitochondrial-complex-iii-activity-and-accelerates-supercomplex-formation
#15
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)...
January 1, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/27912063/structure-of-mammalian-respiratory-supercomplex-i1iii2iv1
#16
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
#17
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
#18
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
#19
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 24, 2016: Nature
https://www.readbyqxmd.com/read/27799543/complex-i-assembly-into-supercomplexes-determines-differential-mitochondrial-ros-production-in-neurons-and-astrocytes
#20
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
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