Complex I assembly into supercomplexes determines differential mitochondrial ROS production in neurons and astrocytes.

TitleComplex I assembly into supercomplexes determines differential mitochondrial ROS production in neurons and astrocytes.
Publication TypeJournal Article
Year of Publication2016
AuthorsLopez-Fabuel, I, Le Douce, J, Logan, A, James, AM, Bonvento, G, Murphy, MP, Almeida, A, Bolaños, JP
JournalProc Natl Acad Sci U S A
Volume113
Issue46
Pagination13063-13068
Date Published2016 Nov 15
ISSN1091-6490
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.

DOI10.1073/pnas.1613701113
Alternate JournalProc. Natl. Acad. Sci. U.S.A.
Citation Key10.1073/pnas.1613701113
PubMed ID27799543
PubMed Central IDPMC5135366
Grant ListMC_U105663142 / / Medical Research Council / United Kingdom
R21 DA037678 / DA / NIDA NIH HHS / United States