Journal article
COA6 is a mitochondrial complex IV assembly factor critical for biogenesis of mtDNA-encoded COX2
DA Stroud, MJ Maher, C Lindau, FN Vögtle, AE Frazier, E Surgenor, H Mountford, AP Singh, M Bonas, S Oeljeklaus, B Warscheid, C Meisinger, DR Thorburn, MT Ryan
Human Molecular Genetics | Published : 2015
DOI: 10.1093/hmg/ddv265
Abstract
Biogenesis of complex IV of the mitochondrial respiratory chain requires assembly factors for subunit maturation, co-factor attachment and stabilization of intermediate assemblies. Apathogenic mutation in COA6, leading to substitution of a conserved tryptophan for a cysteine residue, results in a loss of complex IV activity and cardiomyopathy. Here, we demonstrate that the complex IV defect correlates with a severe loss in complex IV assembly in patient heart but not fibroblasts. Complete loss of COA6 activity using gene editing in HEK293T cells resulted in a profound growth defect due to complex IV deficiency, caused by impaired biogenesis of the copper-bound mitochondrial DNA-encoded subun..
View full abstractGrants
Awarded by Australian Research Council
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.), the Australian Mitochondrial Disease Foundation (AMDF), the Australian Research Council (ARC Grant DP140102746 to M.J.M.) and the Victorian Government's Operational Infrastructure Support Program. Research in the BW laboratory is supported by the Deutsche Forschungsgemeinschaft and the Excellence Initiative of the German Federal & State Governments (EXC 294 BIOSS).