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.

酰基甘油激酶（AGK）是一种线粒体脂质激酶，可催化单酰基甘油和二酰基甘油分别磷酸化为溶血磷脂酸和磷脂酸。AGK中的突变引起Sengers综合征，其特征为先天性白内障，肥厚型心肌病，骨骼肌病，运动不耐症和乳酸性酸中毒。在这里，我们确定了AGK为线粒体TIM22蛋白输入复合体的一个亚基。我们表明，AGK以激酶独立的方式发挥功能，以维持TIM22复合物的完整性，从而促进线粒体载体蛋白的导入和组装。分离自Sengers综合征患者细胞和组织的线粒体显示不稳定的TIM22复合物和载体底物的生物发生缺陷。与此表型一致，我们观察到缺乏AGK的细胞在三羧酸（TCA）周期中出现扰动。