Arginine catabolism involves enzyme-dependent reactions in both mitochondria and the cytosol, defects in which may lead to hyperargininemia, a devastating developmental disorder. It is largely unknown if defective arginine catabolism has any effects on mitochondria. Here we report that normal arginine catabolism is essential for mitochondrial homeostasis in Caenorhabditis elegans. Mutations of the arginase gene argn-1 lead to abnormal mitochondrial enlargement and reduced adenosine triphosphate (ATP) production in C. elegans hypodermal cells. ARGN-1 localizes to mitochondria and its loss causes arginine accumulation, which disrupts mitochondrial dynamics. Heterologous expression of human ARG1 or ARG2 rescued the mitochondrial defects of argn-1 mutants. Importantly, genetic inactivation of the mitochondrial basic amino acid transporter SLC-25A29 or the mitochondrial glutamate transporter SLC-25A18.1 fully suppressed the mitochondrial defects caused by argn-1 mutations. These findings suggest that mitochondrial damage probably contributes to the pathogenesis of hyperargininemia and provide clues for developing therapeutic treatments for hyperargininemia.

精氨酸分解代谢涉及线粒体和胞质溶胶中的酶依赖性反应，其中的缺陷可能导致高精氨酸血症，这是毁灭性的发育障碍。有缺陷的精氨酸分解代谢是否会对线粒体产生任何影响，这一点在很大程度上是未知的。在这里，我们报告说，正常的精氨酸分解代谢是在线粒体动态平衡至关重要Ç aenorhabditis 线虫。精氨酸酶基因的突变ARGN-1导致线粒体异常增大和降低的三磷酸腺苷（ATP）在生产线虫下皮细胞。ARGN-1定位于线粒体，其丢失会导致精氨酸积累，从而破坏线粒体动力学。人类ARG1或ARG2的异源表达挽救了argn-1突变体的线粒体缺陷。重要的是，线粒体碱性氨基酸转运蛋白SLC-25A29或线粒体谷氨酸转运蛋白SLC-25A18.1的遗传失活完全抑制了由argn-1突变引起的线粒体缺陷。这些发现表明线粒体损伤可能促进了高精氨酸血症的发病，并为开发高精氨酸血症的治疗方法提供了线索。