Journal article

Characterization of mitochondrial FOXRED1 in the assembly of respiratory chain complex I

Luke E Formosa, Masakazu Mimaki, Ann E Frazier, Matthew McKenzie, Tegan L Stait, David R Thorburn, David A Stroud, Michael T Ryan

Human Molecular Genetics | OXFORD UNIV PRESS | Published : 2015


Human mitochondrial complex I is the largest enzyme of the respiratory chain and is composed of 44 different subunits. Complex I subunits are encoded by both nuclear and mitochondrial (mt) DNA and their assembly requires a number of additional proteins. FAD-dependent oxidoreductase domain-containing protein 1 (FOXRED1) was recently identified as a putative assembly factor and FOXRED1 mutations in patients cause complex I deficiency; however, its role in assembly is unknown. Here, we demonstrate that FOXRED1 is involved in mid-late stages of complex I assembly. In a patient with FOXRED1 mutations, the levels of mature complex I were markedly decreased, and a smaller ∼475 kDa subcomplex was de..

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Funding Acknowledgements

This work was supported by Australian National Health and Medical Research Council grants (to M.T.R., D.A.S. and D.R.T.) and Fellowships (Early Career Fellowship to D.A.S., Career Development Fellowship to A.E.F., Principal Research Fellowship to D.R.T.), Australian Research Council Future Fellowship (to M.Mc.K.), the Australian Mitochondrial Disease Foundation (AMDF), the Victorian Government's Operational Infrastructure Support Program and JSPS KAKENHI (Grant number 25461539 to M.M.).