Mitochondrial COA7 is a heme-binding protein with disulfide reductase activity, which acts in the early stages of complex IV assembly

LE Formosa; S Maghool; AJ Sharpe; B Reljic; L Muellner-Wong; DA Stroud; MT Ryan; MJ Maher

Journal article

Mitochondrial COA7 is a heme-binding protein with disulfide reductase activity, which acts in the early stages of complex IV assembly

LE Formosa, S Maghool, AJ Sharpe, B Reljic, L Muellner-Wong, DA Stroud, MT Ryan, MJ Maher

Proceedings of the National Academy of Sciences of the United States of America | Published : 2022

DOI: 10.1073/pnas.2110357119

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Abstract

Cytochrome c oxidase (COX) assembly factor 7 (COA7) is a metazoan-specific assembly factor, critical for the biogenesis of mitochondrial complex IV (cytochrome c oxidase). Although mutations in COA7 have been linked to complex IV assembly defects and neurological conditions such as peripheral neuropathy, ataxia, and leukoencephalopathy, the precise role COA7 plays in the biogenesis of complex IV is not known. Here, we show that loss of COA7 blocks complex IV assembly after the initial step where the COX1 module is built, progression from which requires the incorporation of copper and addition of the COX2 and COX3 modules. The crystal structure of COA7, determined to 2.4 Å resolution, reveals..

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University of Melbourne Researchers

Shadi Maghool Author

David Stroud Author

Megan Maher Author

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Awarded by Australian Research Council

Funding Acknowledgements

This study was funded by the Australian Research Council (DP140102746 and FT180100397 to M.J.M. and DP220102030 to M.J.M. and M.T.R.) , the National Health and Medical Research Council (GNT1165217 to M.T.R. and M.J.M., GNT1140906 and GNT1140851 to D.A.S., and GNT2010149 to L.E.F.) , and an Australian Government Research Training Program Scholarship to S.M. L.E.F. also acknowledges support from the Mito Foundation. Part of this study was carried out using the MX2 beamline at the Australian Synchrotron, which is part of the Australian Nuclear Science and Technology Organisation (ANSTO) , and made use of the Australian Cancer Research Foundation (ACRF) detector. We thank the beamline staff for their enthusiastic and professional support, Dr. Yee-Foong Mok at the Melbourne Protein characterization facility, the Bio21 Molecular Science and Biotechnol-ogy Institute for performing the AUC experiments and data analyses, the Bio21 Mass Spectrometry and Proteomics Facility for the provision of instru-mentation, training, and technical support, Daniel Machell for PyMOL and coding assistance, Dr. Katie Ganio and Prof. Christopher McDevitt for the ICP-MS analysis, and Mrs. Mahnaz Dideh Var for her extraordinary support with the structural biology aspects of this study. We thank the reviewers for their constructive comments. Schematics were created using Biorender.com .