Journal article

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

Luke E Formosa, Linden Muellner-Wong, Boris Reljic, Alice J Sharpe, Thomas D Jackson, Traude H Beilharz, Diana Stojanovski, Michael Lazarou, David A Stroud, Michael T Ryan

Cell Reports | CELL PRESS | Published : 2020

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 co..

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Grants

Awarded by National Health and Medical Research Council (NHMRC)


Awarded by Australian Research Council


Funding Acknowledgements

We thank lab members for constructive discussions, the Bio21 Mass Spectrometry and Proteomics Facility (MMSPF), the Monash Proteomics and Metabolomics Facility (MPMF) for the provision of instrumentation, training, and technical support, and Monash Flowcore for cell sorting. T.D.J. is supported by an Australian Government Research Training Program (RTP) Scholarship. We acknowledge funding from the National Health and Medical Research Council (NHMRC project grants 1164459 to M.T.R., 1125390 and 1140906 to M.T.R. and D.A.S., and NHMRC Fellowship 1140851 to D.A.S.), a Research Fellowship from the Mito Foundation, and funding from the Australian Research Council (DP170101249 to D.S.).