한빛사논문
- 조회756
Isaac Park1,9, Kwang-eun Kim 1,2,9, Jeesoo Kim3,4,9, Ae-Kyeong Kim5, Subin Bae6, Minkyo Jung7, Jinhyuk Choi2, Pratyush Kumar Mishra 1, Taek-Min Kim2, Chulhwan Kwak1, Myeong-Gyun Kang1, Chang-Mo Yoo1, Ji Young Mun7, Kwang-Hyeon Liu6, Kyu-Sun Lee 5,8, Jong-Seo Kim 3,4, Jae Myoung Suh 2 & Hyun-Woo Rhee 1,3
1Department of Chemistry, Seoul National University, Seoul, Republic of Korea.
2Graduate School of Medical Science and Engineering, KAIST, Daejeon, Republic of Korea.
3School of Biological Sciences, Seoul National University, Seoul, Republic of Korea.
4Center for RNA Research, Institute for Basic Science, Seoul, Republic of Korea.
5Metabolism and Neurophysiology Research Group, KRIBB, Daejeon, Republic of Korea.
6BK21 FOUR Community-Based Intelligent Novel Drug Discovery Education Unit, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, Korea.
7Neural Circuit Research Group, Korea Brain Research Institute, Daegu, Republic of Korea.
8School of Pharmacy, Sungkyunkwan University, Suwon, Korea.
9These authors contributed equally: Isaac Park, Kwang-eun Kim, Jeesoo Kim.
Corresponding authors : Correspondence to Kyu-Sun Lee, Jong-Seo Kim, Jae Myoung Suh or Hyun-Woo Rhee.
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.
논문정보
- Research article
- 2023년 10월 (BRIC 등록일 2023-10-27)
- 국내 연구진
- 생명과학 > 세포생물학
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