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dc.contributor.authorJackson, TD
dc.contributor.authorHock, DH
dc.contributor.authorFujihara, KM
dc.contributor.authorPalmer, CS
dc.contributor.authorFrazier, AE
dc.contributor.authorLow, YC
dc.contributor.authorKang, Y
dc.contributor.authorAng, C-S
dc.contributor.authorClemons, NJ
dc.contributor.authorThorburn, DR
dc.contributor.authorStroud, DA
dc.contributor.authorStojanovski, D
dc.date.accessioned2021-07-13T23:10:52Z
dc.date.available2021-07-13T23:10:52Z
dc.date.issued2021-03-15
dc.identifier.citationJackson, T. D., Hock, D. H., Fujihara, K. M., Palmer, C. S., Frazier, A. E., Low, Y. C., Kang, Y., Ang, C. -S., Clemons, N. J., Thorburn, D. R., Stroud, D. A. & Stojanovski, D. (2021). The TIM22 complex mediates the import of sideroflexins and is required for efficient mitochondrial one-carbon metabolism. MOLECULAR BIOLOGY OF THE CELL, 32 (6), pp.475-491. https://doi.org/10.1091/mbc.E20-06-0390.
dc.identifier.issn1059-1524
dc.identifier.urihttp://hdl.handle.net/11343/278203
dc.description.abstractAcylglycerol 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 down-regulation of SFXN proteins, which contain five transmembrane domains, and show that they represent a novel class of TIM22 complex substrate. Perturbed biogenesis of SFXN proteins in cells lacking AGK reduces the proliferative capabilities of these cells in the absence of exogenous serine, suggesting that dysregulation of one-carbon metabolism is a molecular feature in the biology of Sengers syndrome.
dc.languageEnglish
dc.publisherAMER SOC CELL BIOLOGY
dc.rights.urihttps://creativecommons.org/licenses/by-nc-sa/4.0
dc.titleThe TIM22 complex mediates the import of sideroflexins and is required for efficient mitochondrial one-carbon metabolism
dc.typeJournal Article
dc.identifier.doi10.1091/mbc.E20-06-0390
melbourne.affiliation.departmentSir Peter MacCallum Department of Oncology
melbourne.affiliation.departmentBiochemistry and Molecular Biology
melbourne.affiliation.departmentBio21
melbourne.affiliation.facultyMedicine, Dentistry & Health Sciences
melbourne.affiliation.facultyAffiliate
melbourne.source.titleMolecular Biology of the Cell
melbourne.source.volume32
melbourne.source.issue6
melbourne.source.pages475-491
melbourne.identifier.nhmrc1140851
melbourne.identifier.nhmrc1140906
melbourne.identifier.arcDP170101249
dc.rights.licenseCC BY-NC-SA
melbourne.elementsid1490836
melbourne.contributor.authorAng, Ching-Seng
melbourne.contributor.authorStojanovski, Diana
melbourne.contributor.authorClemons, Nicholas
melbourne.contributor.authorPalmer, Catherine
melbourne.contributor.authorStroud, David
melbourne.contributor.authorFujihara, Kenji
dc.identifier.eissn1939-4586
melbourne.identifier.fundernameidAustralian Research Council, DP170101249
melbourne.identifier.fundernameidNHMRC, 1140851
melbourne.identifier.fundernameidNHMRC, 1140906
melbourne.accessrightsOpen Access


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