Respiratory supercomplexes act as a platform for complex III-mediated maturation of human mitochondrial complexes I and IV.

TitleRespiratory supercomplexes act as a platform for complex III-mediated maturation of human mitochondrial complexes I and IV.
Publication TypeJournal Article
Year of Publication2020
AuthorsProtasoni, M, Pérez-Pérez, R, Lobo-Jarne, T, Harbour, ME, Ding, S, Peñas, A, Diaz, F, Moraes, CT, Fearnley, IM, Zeviani, M, Ugalde, C, Fernandez-Vizarra, E
JournalEMBO J
Paginatione102817
Date Published2020 Jan 08
ISSN1460-2075
Abstract

Mitochondrial respiratory chain (MRC) enzymes associate in supercomplexes (SCs) that are structurally interdependent. This may explain why defects in a single component often produce combined enzyme deficiencies in patients. A case in point is the alleged destabilization of complex I in the absence of complex III. To clarify the structural and functional relationships between complexes, we have used comprehensive proteomic, functional, and biogenetical approaches to analyze a MT-CYB-deficient human cell line. We show that the absence of complex III blocks complex I biogenesis by preventing the incorporation of the NADH module rather than decreasing its stability. In addition, complex IV subunits appeared sequestered within complex III subassemblies, leading to defective complex IV assembly as well. Therefore, we propose that complex III is central for MRC maturation and SC formation. Our results challenge the notion that SC biogenesis requires the pre-formation of fully assembled individual complexes. In contrast, they support a cooperative-assembly model in which the main role of complex III in SCs is to provide a structural and functional platform for the completion of overall MRC biogenesis.

DOI10.15252/embj.2019102817
Alternate JournalEMBO J.
Citation Key10.15252/embj.2019102817
PubMed ID31912925
Grant ListMC_UU_00015/5 / / UK Research and Innovation|Medical Research Council (MRC) /
FP7-3222424 / / EC|FP7|FP7 Ideas: European Research Council (FP7 Ideas) /
16086 / / French Muscular Dystrophy Association (AFM-Téléthon) /
PI17-00048 / / MEC|Instituto de Salud Carlos III (ISCIII) /
P2018/BAA-4403 / / Comunidad de Madrid (Madrid Autonomous Community) /
GM105781 / / HHS|National Institutes of Health (NIH) /