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

Isaac ParkKwang-Eun KimJeesoo KimAe-Kyeong KimSubin BaeMinkyo JungJinhyuk ChoiPratyush Kumar MishraTaek-Min KimChulhwan KwakMyeong-Gyun KangChang-Mo YooJi Young MunKwang-Hyeon LiuKyu-Sun LeeJong-Seo KimJae Myoung SuhHyun-Woo Rhee
Published in: Nature chemical biology (2023)
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 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.
Keyphrases
  • oxidative stress
  • skeletal muscle
  • gene expression
  • cancer therapy
  • small molecule
  • nitric oxide
  • high throughput
  • reactive oxygen species
  • genome wide
  • protein protein
  • amino acid
  • protein kinase