The TIM22 complex mediates the import of sideroflexins and is required for efficient mitochondrial one-carbon metabolism
| Autor: | David R. Thorburn, Yilin Kang, Kenji M Fujihara, Catherine S Palmer, Yau C Low, Ann E. Frazier, Nicholas J. Clemons, Daniella H Hock, David A. Stroud, Thomas Daniel Jackson, Diana Stojanovski, Ching-Seng Ang |
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| Rok vydání: | 2021 |
| Předmět: |
Proteomics
Protein subunit Primary Cell Culture Cell Culture Techniques Mitochondrion Mitochondrial Membrane Transport Proteins Mitochondrial Proteins 03 medical and health sciences Mitochondrial membrane transport protein 0302 clinical medicine Mitochondrial Precursor Protein Import Complex Proteins Humans Inner mitochondrial membrane Molecular Biology 030304 developmental biology 0303 health sciences biology Membrane transport protein Membrane Proteins Membrane Transport Proteins Articles Cell Biology Carbon Mitochondria Cell biology Phosphotransferases (Alcohol Group Acceptor) Phenotype Membrane protein Mitochondrial Membranes Mutation MCF-7 Cells biology.protein Carrier Proteins Acylglycerol kinase 030217 neurology & neurosurgery Biogenesis |
| Zdroj: | Molecular Biology of the Cell |
| ISSN: | 1939-4586 1059-1524 |
| DOI: | 10.1091/mbc.e20-06-0390 |
| Popis: | 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 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. |
| Databáze: | OpenAIRE |
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