Protasoni 2020 EMBO J

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Protasoni M, Pérez-Pérez R, Lobo-Jarne T, Harbour ME, Ding S, Peñas A, Diaz F, Moraes CT, Fearnley IM, Zeviani M, Ugalde C, Fernández-Vizarra E (2020) Respiratory supercomplexes act as a platform for complex III-mediated maturation of human mitochondrial complexes I and IV. EMBO J 39:e102817.

» PMID: 31912925 Open Access

Protasoni M, Perez-Perez R, Lobo-Jarne T, Harbour ME, Ding S, Penas A, Diaz F, Moraes CT, Fearnley IM, Zeviani M, Ugalde C, Fernandez-Vizarra E (2020) EMBO J

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.

© 2020 The Authors. Published under the terms of the CC BY 4.0 license.

Keywords: Complex I, Complex III, Cytochrome b mutation, Mitochondrial respiratory chain assembly, Supercomplexes Bioblast editor: Plangger M O2k-Network Lab: US FL Miami Moraes CT


Labels: MiParea: Respiration, mt-Membrane 


Organism: Human  Tissue;cell: Other cell lines  Preparation: Intact cells  Enzyme: Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase, Supercomplex 

Coupling state: LEAK, ROUTINE, ET  Pathway: ROX  HRR: Oxygraph-2k 

Labels, 2020-01