Kang 2017 Mol Cell
|Kang Y, Stroud DA, Baker MJ, De Souza DP, Frazier AE, Liem M, Tull D, Mathivanan S, McConville MJ, Thorburn DR, Ryan MT, Stojanovski D (2017) Sengers Syndrome-associated mitochondrial acylglycerol kinase is a subunit of the human TIM22 protein import complex. Mol Cell 67:457-70.|
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 cells and tissues show a destabilized TIM22 complex and defects in the biogenesis of carrier substrates. Consistent with this phenotype, we observe perturbations in the tricarboxylic acid (TCA) cycle in cells lacking AGK. Our identification of AGK as a bona fide subunit of TIM22 provides an exciting and unexpected link between mitochondrial protein import and Sengers syndrome.
• Keywords: mitochondria, lipid metabolism, protein transport, TIM22 complex, mitochondrial carrier proteins, Sengers syndrome, TCA cycle, acylglycerol kinase, AGK • Bioblast editor: Gnaiger E • O2k-Network Lab: AU Clayton St John J
Labels: MiParea: Respiration, nDNA;cell genetics, mt-Medicine Pathology: Inherited, Other
Preparation: Intact cells Enzyme: Inner mt-membrane transporter
Coupling state: ROUTINE, ET