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Mitochondrial matrix RTN4IP1/OPA10 is an oxidoreductase for coenzyme Q synthesis

Cited 4 time in Web of Science Cited 5 time in Scopus
Authors

Park, Isaac; Kim, Kwang-eun; Kim, Jeesoo; Kim, Ae-Kyeong; Bae, Subin; Jung, Minkyo; Choi, Jinhyuk; Mishra, Pratyush Kumar; Kim, Taek-Min; Kwak, Chulhwan; Kang, Myeong-Gyun; Yoo, Chang-Mo; Mun, Ji Young; Liu, Kwang-Hyeon; Lee, Kyu-Sun; Kim, Jong-Seo; Suh, Jae Myoung; Rhee, Hyun-Woo

Issue Date
2024-02
Publisher
Nature Publishing Group
Citation
Nature Chemical Biology, Vol.20 No.2, pp.221-233
Abstract
Targeting proximity-labeling enzymes to specific cellular locations is a viable strategy for profiling subcellular proteomes. Here, we generated transgenic mice (MAX-Tg) expressing a mitochondrial matrix-targeted ascorbate peroxidase. Comparative analysis of matrix proteomes from the muscle tissues showed differential enrichment of mitochondrial proteins. We found that reticulon 4-interacting protein 1 (RTN4IP1), also known as optic atrophy-10, is enriched in the mitochondrial matrix of muscle tissues and is an NADPH oxidoreductase. Interactome analysis and in vitro enzymatic assays revealed an essential role for RTN4IP1 in coenzyme Q (CoQ) biosynthesis by regulating the O-methylation activity of COQ3. Rtn4ip1-knockout myoblasts had markedly decreased CoQ9 levels and impaired cellular respiration. Furthermore, muscle-specific knockdown of dRtn4ip1 in flies resulted in impaired muscle function, which was reversed by dietary supplementation with soluble CoQ. Collectively, these results demonstrate that RTN4IP1 is a mitochondrial NAD(P)H oxidoreductase essential for supporting mitochondrial respiration activity in the muscle tissue. The development of a transgenic mouse line that expresses mitochondrial matrix-targeted APEX2 combined with proteome analysis identified RTN4IP1, which serves as an NAD(P)H oxidoreductase required for respiration and CoQ biosynthesis.
ISSN
1552-4450
URI
https://hdl.handle.net/10371/201873
DOI
https://doi.org/10.1038/s41589-023-01452-w
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  • College of Natural Sciences
  • School of Biological Sciences
Research Area Molecular Interactomics, Proteomics, Systems Biology, 단백체학, 분자상호작용체학, 시스템생물학

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