Defective arginine metabolism impairs mitochondrial homeostasis in Caenorhabditis elegans  

作　　者：Ruofeng Tang Xin Wang Junxiang Zhou Fengxia Zhang Shan Zhao Qiwen Gan Liyuan Zhao Fengyang Wang Qian Zhang Jie Zhang Guodong Wang Chonglin Yang 

机构地区：[1]State Key Laboratory of Natural Resource Conservation and Utilization in Yunnan,Center for Life Science,School of Life Sciences,Yunnan University,Kunming,650021,China [2]State Key Laboratory of Molecular Developmental Biology,Institute of Genetics and Developmental Biology,Chinese Academy of Sciences,Beijing,100101,China [3]Graduate University of Chinese Academy of Sciences,Beijing,100049,China [4]State Key Laboratory of Plant Genomics,Institute of Genetics and Developmental Biology,Chinese Academy of Sciences,Beijing,100101,China

出　　处：《Journal of Genetics and Genomics》2020年第3期145-156,共12页遗传学报（英文版）

基　　金：supported by grants from the National Scicnce Foundation of China(91954204 and 31730053);the National Basic Research Program of China(2017YFA0503403)。

摘　　要：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 ARGl 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.

关 键 词：ARGININE ARGINASE Hyperargininemia Mitochondrial homeostasis C.elegans 

分 类 号：R589[医药卫生—内分泌]