AGK human LC-MSMS project part I (proteome)

Mutations in the mitochondrial acylglycerol kinase AGK cause Sengers syndrome characterized by cataracts, hypertrophic cardiomyopathy and skeletal myopathy. AGK generates phosphatidic acid and lyso-phosphatidic acid, bioactive phospholipids involved in lipid signaling and the regulation of tumor progression. However, molecular mechanisms of the mitochondrial pathology remain enigmatic. Determining its mitochondrial interactome, we have identified AGK as a constituent of the TIM22 protein translocase in the mitochondrial inner membrane. AGK assembles with TIMM22 and TIMM29 and supports the import of a subset of multi-spanning membrane proteins. The function of AGK as subunit of the TIM22 translocase does not depend on its kinase activity. However, enzymatically active AGK is required to maintain mitochondrial cristae morphogenesis and the apoptotic resistance of cells. The dual function of AGK as lipid kinase and constituent of the TIM22 translocase reveals that disturbances in both phospholipid metabolism and mitochondrial protein biogenesis contribute to the pathogenesis of Sengers syndrome. See the published paper for more information of the experimental setup.