Journal article

The TIM22 complex mediates the import of sideroflexins and is required for efficient mitochondrial one-carbon metabolism

Thomas D Jackson, Daniella H Hock, Kenji M Fujihara, Catherine S Palmer, Ann E Frazier, Yau C Low, Yilin Kang, Ching-Seng Ang, Nicholas J Clemons, David R Thorburn, David A Stroud, Diana Stojanovski



Acylglycerol kinase (AGK) is a mitochondrial lipid kinase that contributes to protein biogenesis as a subunit of the TIM22 complex at the inner mitochondrial membrane. Mutations in AGK cause Sengers syndrome, an autosomal recessive condition characterized by congenital cataracts, hypertrophic cardiomyopathy, skeletal myopathy, and lactic acidosis. We mapped the proteomic changes in Sengers patient fibroblasts and AGKKO cell lines to understand the effects of AGK dysfunction on mitochondria. This uncovered down-regulation of a number of proteins at the inner mitochondrial membrane, including many SLC25 carrier family proteins, which are predicted substrates of the complex. We also observed do..

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Awarded by Australian Research Council

Awarded by National Health and Medical Research Council (NHMRC)

Awarded by Victorian Government Department of Health and Human Services through the Victorian Cancer Agency

Funding Acknowledgements

T.D.J. and K.M.F. are supported by Australian Government Research Training Program (RTP) scholarships. D.H.H. is supported by a Melbourne International Research Scholarship. T.D.J., D.H.H., and Y.C.L are supported by Australian Mito Foundation PhD TopUp scholarships. D.S. is supported by a Research Fellowship from the Mito Foundation. We acknowledge funding from the Australian Research Council (DP170101249 to D.S.), the National Health and Medical Research Council (NHMRC Project Grant 1140906 to D.A.S.; NHMRC Fellowship 1140851 to D.A.S; and NHMRC Fellowship 1155244 to D.R.T), the Australian Mito Foundation (D.R.T., A.E.F., and D.S.); and the Victorian Government's Operational Infrastructure Support Program (D.R.T). Nicholas J. Clemons is supported by a Fellowship (MCRF16002) from the Victorian Government Department of Health and Human Services acting through the Victorian Cancer Agency. We thank Kristin Brown (Peter MacCallum Cancer Centre) for providing us with serine and glycine free DMEM.