Defective arginine metabolism impairs mitochondrial homeostasis in Caenorhabditis elegans

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

doi:10.1016/j.jgg.2020.02.007

Volume 47 Issue 3

Mar. 2020

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Defective arginine metabolism impairs mitochondrial homeostasis in Caenorhabditis elegans

doi: 10.1016/j.jgg.2020.02.007

Ruofeng Tang^{a, b, c},
Xin Wang^c,
Junxiang Zhou^{a, b, c},
Fengxia Zhang^d,
Shan Zhao^c,
Qiwen Gan^{a, b, c},
Liyuan Zhao^{a, b},
Fengyang Wang^{a, b},
Qian Zhang^{a, b},
Jie Zhang^c,
Guodong Wang^d,
Chonglin Yang^a

a
State Key Laboratory of Natural Resource Conservation and Utilization in Yunnan, Center for Life Science, School of Life Sciences, Yunnan University, Kunming, 650021, China
b
State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China
c
Graduate University of Chinese Academy of Sciences, Beijing, 100049, China
d
State Key Laboratory of Plant Genomics, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China

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Corresponding 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.
- Arginine,
- Arginase,
- Hyperargininemia,
- Mitochondrial homeostasis

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References(38)

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