Mitochondrial Matrix RTN4IP1/OPA10 is an Oxidoreductase for Coenzyme Q Synthesis

Overview

Journal Nat Chem Biol

Specialties Biochemistry
Biology
Chemistry

Date 2023 Oct 26

PMID 37884807

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

Affiliations

Soon will be listed here.

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 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.

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