Sengers Syndrome-Associated Mitochondrial Acylglycerol Kinase Is a Subunit of the Human TIM22 Protein Import Complex

Y Kang; DA Stroud; MJ Baker; DP De Souza; AE Frazier; M Liem; D Tull; S Mathivanan; MJ McConville; DR Thorburn; MT Ryan; D Stojanovski

Journal article

Sengers Syndrome-Associated Mitochondrial Acylglycerol Kinase Is a Subunit of the Human TIM22 Protein Import Complex

Y Kang, DA Stroud, MJ Baker, DP De Souza, AE Frazier, M Liem, D Tull, S Mathivanan, MJ McConville, DR Thorburn, MT Ryan, D Stojanovski

Molecular Cell | CELL PRESS | Published : 2017

DOI: 10.1016/j.molcel.2017.06.014

Abstract

Acylglycerol kinase (AGK) is a mitochondrial lipid kinase that catalyzes the phosphorylation of monoacylglycerol and diacylglycerol to lysophosphatidic acid and phosphatidic acid, respectively. Mutations in AGK cause Sengers syndrome, which is characterized by congenital cataracts, hypertrophic cardiomyopathy, skeletal myopathy, exercise intolerance, and lactic acidosis. Here we identified AGK as a subunit of the mitochondrial TIM22 protein import complex. We show that AGK functions in a kinase-independent manner to maintain the integrity of the TIM22 complex, where it facilitates the import and assembly of mitochondrial carrier proteins. Mitochondria isolated from Sengers syndrome patient c..

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University of Melbourne Researchers

Yilin Kang Author

David Stroud Author

David de Souza Author

Ann Frazier Author

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Grants

Awarded by Australian Mitochondrial Disease Foundation

Funding Acknowledgements

Y.K. is supported by Melbourne International Fee Remission Scholarship (MIFRS) and Melbourne International Research Scholarship (MIRS). D.S. is supported by the Biochemistry Fund Fellowship through the Department of Biochemistry and Molecular Biology, The University of Melbourne. We acknowledge funding from the Australian Research Council DP170101249 (to D.S.), NHMRC Project Grants 1125390 and 1107094 (to M.T.R., D.R.T., and D.A.S.), the Australian Mitochondrial Disease Foundation, and the Victorian Government's Operational Infrastructure Support Program. D.A.S. is an NHMRC Early Career Research Fellow (1070916) and M.J.M. (1059530) and D.R.T. (1022896) are NHMRC Principal Research Fellows.