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Respiratory supercomplexes act as a platform for complex III ‐mediated maturation of human mitochondrial complexes I and IV
Author(s) -
Protasoni Margherita,
PérezPérez Rafael,
LoboJarne Teresa,
Harbour Michael E,
Ding Shujing,
Peñas Ana,
Diaz Francisca,
Moraes Carlos T,
Fearnley Ian M,
Zeviani Massimo,
Ugalde Cristina,
FernándezVizarra Erika
Publication year - 2020
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.2019102817
Subject(s) - biogenesis , mitochondrial biogenesis , coenzyme q – cytochrome c reductase , mitochondrion , microbiology and biotechnology , respiratory chain , complex formation , chemistry , biology , biochemistry , inorganic chemistry , cytochrome c , gene
Mitochondrial respiratory chain ( MRC ) enzymes associate in supercomplexes ( SC s) 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 SC s is to provide a structural and functional platform for the completion of overall MRC biogenesis.