Year: 2023
Type: article
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 CoQ 9 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.
Source: Nature Chemical Biology
Authors: Isaac Park, Kwang-eun Kim, Jeesoo Kim, Ae-Kyeong Kim, Subin Bae, Minkyo Jung, Jinhyuk Choi, Pratyush Kumar Mishra, Taek-Min Kim, Chulhwan Kwak, Myeong-Gyun Kang, Chang-Mo Yoo, Ji Young Mun, Kwang-Hyeon Liu, Kyu-Sun Lee, Jong-Seo Kim, Jae Myoung Suh, Hyun-Woo Rhee
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $11,690
Funders: Korea Brain Research Institute, National Research Foundation, Seoul National University, Korea Health Industry Development Institute, Korea Research Institute of Bioscience and Biotechnology, National Research Foundation of Korea, Korea Advanced Institute of Science and Technology, Institute for Basic Science, Ministry of Science and ICT, South Korea, Samsung Science and Technology Foundation, Samsung, Korea Evaluation Institute of Industrial Technology
Awards: G1346571950, G138333412, G1442093329, G1492580079, G1551050494, G1581234594, G1622723095, G1799564886, G1802548948, G2006193230, G2169336704, G2214948142, G2304812787, G2337071106, G2402660949, G2643796712, G322481348, G3264138898, G3969051666, G4001076239, G4021957986, G4529589349, G4600871193, G5201466859, G5417615882, G5433976708, G5526961238, G5598398694, G5631362762, G5711340399, G6021703449, G6127215812, G6310749854, G6778206002, G7572747708, G7750438674, G8099688578, G8434136596, G848733465, G8661181119, G8739444332
OpenAlex ID: W4387965110