title: Complex I assembly into supercomplexes determines differential mitochondrial ROS production in neurons and astrocytes.
abstract: 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. The presence of free complex I in astrocytes correlates with the severalfold higher reactive oxygen species (ROS) production by astrocytes compared with neurons. Using a complexomics approach, we found that the complex I subunit NDUFS1 was more abundant in neurons than in astrocytes. Interestingly, NDUFS1 knockdown in neurons decreased the association of complex I into supercomplexes, leading to impaired oxygen consumption and increased mitochondrial ROS. Conversely, overexpression of NDUFS1 in astrocytes promoted complex I incorporation into supercomplexes, decreasing ROS. Thus, complex I assembly into supercomplexes regulates ROS production and may contribute to the bioenergetic differences between neurons and astrocytes.
authors: Institute of Functional Biology and Genomics, University of Salamanca-Consejo Superior de Investigaciones Cientificas, 37007 Salamanca, Spain.
authors: Irene
authors: 0000-0002-3049-748X
authors: I
authors: Lopez-Fabuel
authors: Commissariat à l'Energie Atomique et aux Energies Alternatives, Département des Sciences du Vivant, Institut d'Imagerie Biomédicale, Molecular Imaging Center, CNRS UMR 9199, Université Paris-Sud, Université Paris-Saclay, F-92260 Fontenay-aux-Roses, France.
authors: Juliette
authors: J
authors: Le Douce
authors: Medical Research Council Mitochondrial Biology Unit, Cambridge Biomedical Campus, Cambridge CB2 0XY, United Kingdom.
authors: Angela
authors: A
authors: Logan
authors: Medical Research Council Mitochondrial Biology Unit, Cambridge Biomedical Campus, Cambridge CB2 0XY, United Kingdom.
authors: Andrew M
authors: AM
authors: James
authors: Commissariat à l'Energie Atomique et aux Energies Alternatives, Département des Sciences du Vivant, Institut d'Imagerie Biomédicale, Molecular Imaging Center, CNRS UMR 9199, Université Paris-Sud, Université Paris-Saclay, F-92260 Fontenay-aux-Roses, France.
authors: Gilles
authors: G
authors: Bonvento
authors: Medical Research Council Mitochondrial Biology Unit, Cambridge Biomedical Campus, Cambridge CB2 0XY, United Kingdom.
authors: Michael P
authors: MP
authors: Murphy
authors: Institute of Biomedical Research of Salamanca, University Hospital of Salamanca, 37007 Salamanca, Spain.
authors: Angeles
authors: 0000-0003-0485-8904
authors: A
authors: Almeida
authors: Institute of Functional Biology and Genomics, University of Salamanca-Consejo Superior de Investigaciones Cientificas, 37007 Salamanca, Spain; jbolanos@usal.es.
authors: Juan P
authors: JP
authors: Bolaños
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D002478:Cells, Cultured; D042967:Electron Transport Complex I / Q000378:metabolism*; D004734:Energy Metabolism; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D042967:Electron Transport Complex I
keywords: bioenergetics; brain; glycolysis; lactate; redox