2. Academic Validation
  3. Dissecting the Roles of Mitochondrial Complex I Intermediate Assembly Complex Factors in the Biogenesis of Complex I

Dissecting the Roles of Mitochondrial Complex I Intermediate Assembly Complex Factors in the Biogenesis of Complex I

  • Cell Rep. 2020 Apr 21;31(3):107541. doi: 10.1016/j.celrep.2020.107541.
Luke E Formosa 1,  Linden Muellner-Wong 2,  Boris Reljic 3,  Alice J Sharpe 2,  Thomas D Jackson 4,  Traude H Beilharz 2,  Diana Stojanovski 4,  Michael Lazarou 2,  David A Stroud 4,  Michael T Ryan 5
Affiliations

Affiliations

  • 1 Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, VIC 3800, Australia. Electronic address: luke.formosa@monash.edu.
  • 2 Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, VIC 3800, Australia.
  • 3 Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, VIC 3800, Australia; Department of Biochemistry and Molecular Biology, The Bio21 Institute, The University of Melbourne, Melbourne, VIC 3000, Australia.
  • 4 Department of Biochemistry and Molecular Biology, The Bio21 Institute, The University of Melbourne, Melbourne, VIC 3000, Australia.
  • 5 Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, VIC 3800, Australia. Electronic address: michael.ryan@monash.edu.
PMID: 32320651 DOI: 10.1016/j.celrep.2020.107541
Abstract

Mitochondrial complex I harbors 7 mitochondrial and 38 nuclear-encoded subunits. Its biogenesis requires the assembly and integration of distinct intermediate modules, mediated by numerous assembly factors. The mitochondrial complex I intermediate assembly (MCIA) complex, containing assembly factors NDUFAF1, ECSIT, ACAD9, and TMEM126B, is required for building the intermediate ND2-module. The role of the MCIA complex and the involvement of other proteins in the biogenesis of this module is unclear. Cell knockout studies reveal that while each MCIA component is critical for complex I assembly, a hierarchy of stability exists centered on ACAD9. We also identify TMEM186 and COA1 as bona fide components of the MCIA complex with loss of either resulting in MCIA complex defects and reduced complex I assembly. TMEM186 enriches with newly translated ND3, and COA1 enriches with ND2. Our findings provide new functional insights into the essential nature of the MCIA complex in complex I assembly.

Keywords

MCIA complex; NADH-ubiquinone dehydrogenase; assembly factors; complex I; mitochondria; oxidative phosphorylation.

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