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Cell Metab. 2017 Jan 10;25(1):128-139. doi: 10.1016/j.cmet.2016.09.002. Epub 2016 Oct 6.

The Assembly Pathway of Mitochondrial Respiratory Chain Complex I.

Author information

1
Molecular Bioenergetics Group, Radboud Center for Mitochondrial Medicine, Department of Pediatrics, Radboud University Medical Center, Geert-Grooteplein Zuid 10, 6525 GA Nijmegen, the Netherlands; Cluster of Excellence Frankfurt Macromolecular Complexes, Goethe-University, Theodor-W.-Adorno-Platz 1, 60323 Frankfurt am Main, Germany.
2
OXPHOS Biogenesis Group, Radboud Center for Mitochondrial Medicine, Department of Pediatrics, Radboud University Medical Center, Geert-Grooteplein Zuid 10, 6525 GA Nijmegen, the Netherlands; Department of General Pediatrics, Neonatology and Pediatric Cardiology, University Children's Hospital, Heinrich-Heine-University, Moorenstrasse 5, 40225 Düsseldorf, Germany.
3
Mitochondrial Neurobiochemistry Group, Radboud Center for Mitochondrial Medicine, Department of Pediatrics, Radboud University Medical Center, Geert-Grooteplein Zuid 10, 6525 GA Nijmegen, the Netherlands.
4
Proteomics Group, Radboud Center for Mitochondrial Medicine, Radboud Proteomics Center, Translational Metabolic Laboratory, Department of Laboratory Medicine, Radboud University Medical Center, Geert-Grooteplein Zuid 10, 6525 GA Nijmegen, the Netherlands.
5
OXPHOS Biogenesis Group, Radboud Center for Mitochondrial Medicine, Department of Pediatrics, Radboud University Medical Center, Geert-Grooteplein Zuid 10, 6525 GA Nijmegen, the Netherlands. Electronic address: leo.nijtmans@radboudumc.nl.

Abstract

Mitochondrial complex I is the largest integral membrane enzyme of the respiratory chain and consists of 44 different subunits encoded in the mitochondrial and nuclear genome. Its biosynthesis is a highly complicated and multifaceted process involving at least 14 additional assembly factors. How these subunits assemble into a functional complex I and where the assembly factors come into play is largely unknown. Here, we applied a dynamic complexome profiling approach to elucidate the assembly of human mitochondrial complex I and its further incorporation into respiratory chain supercomplexes. We delineate the stepwise incorporation of all but one subunit into a series of distinct assembly intermediates and their association with known and putative assembly factors, which had not been implicated in this process before. The resulting detailed and comprehensive model of complex I assembly is fully consistent with recent structural data and the remarkable modular architecture of this multiprotein complex.

KEYWORDS:

assembly; assembly factors; complex I; complexome profiling; mitochondria; oxidative phosporylation

PMID:
27720676
DOI:
10.1016/j.cmet.2016.09.002
[Indexed for MEDLINE]
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