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

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Title
Mitochondrial matrix RTN4IP1/OPA10 is an oxidoreductase for coenzyme Q synthesis
Author(s)
Park, Isaac; Kim, Kwang-eun; Jeesoo Kim; 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; Jong-Seo Kim; Suh, Jae Myoung; Rhee, Hyun-Woo
Publication Date
2024-02
Journal
Nature Chemical Biology, v.20, pp.221 - 233
Publisher
Nature Publishing Group
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 d Rtn4ip1 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. [Figure not available: see fulltext.] © 2023, The Author(s).
URI
https://pr.ibs.re.kr/handle/8788114/14781
DOI
10.1038/s41589-023-01452-w
ISSN
1552-4450
Appears in Collections:
Center for RNA Research(RNA 연구단) > 1. Journal Papers (저널논문)
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