Xin Wang
Junxiang Zhou
Fengxia Zhang
Shan Zhao
Qiwen Gan
Liyuan Zhao
Fengyang Wang
Qian Zhang
Jie Zhang
Guodong Wang
Chonglin Yang
aState Key Laboratory of Natural Resource Conservation and Utilization in Yunnan, Center for Life Science, School of Life Sciences, Yunnan University, Kunming, 650021, China
bState Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China
cGraduate University of Chinese Academy of Sciences, Beijing, 100049, China
dState Key Laboratory of Plant Genomics, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China
More InformationCorresponding author: E-mail address: clyang@ynu.edu.cn (Chonglin Yang)
Publish Date:2020-03-25
Abstract
Abstract
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.Keywords: Arginine,
Arginase,
Hyperargininemia,
Mitochondrial homeostasis
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