Mutations in mitochondrial acylglycerol kinase (AGK) cause Sengers syndrome, which is characterized by cataracts, hypertrophic cardiomyopathy, and skeletal myopathy. AGK generates phosphatidic acid and lysophosphatidic acid, bioactive phospholipids involved in lipid signaling and the regulation of tumor progression. However, the molecular mechanisms of the mitochondrial pathology remain enigmatic. Determining its mitochondrial interactome, we have identified AGK as a constituent of the TIM22 complex 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 a subunit of the TIM22 complex 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 complex reveals that disturbances in both phospholipid metabolism and mitochondrial protein biogenesis contribute to the pathogenesis of Sengers syndrome.

线粒体酰基甘油激酶（AGK）突变会导致Sengers综合征，其特征为白内障，肥厚型心肌病和骨骼肌病。AGK产生磷脂酸和溶血磷脂酸，这些生物活性磷脂与脂质信号传导和肿瘤进程的调节有关。但是，线粒体病理的分子机制仍然是个谜。确定其线粒体相互作用组，我们已经确定AGK是线粒体内膜中TIM22复合物的组成部分。AGK与TIMM22和TIMM29组装在一起，并支持导入多跨膜蛋白。AGK作为TIM22复合物的亚基的功能不取决于其激酶活性。然而，需要具有酶活性的AGK来维持线粒体cr的形态发生和细胞的凋亡抗性。AGK作为脂质激酶和TIM22复合物成分的双重功能表明，磷脂代谢和线粒体蛋白质生物合成的紊乱都有助于Sengers综合征的发病。