Mitochondrial matrix RTN4IP1/OPA10 is an oxidoreductase for coenzyme Q synthesis
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, Jae Myoung Suh, Hyun‐Woo Rhee
Abstract
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.