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Cited by 39Coenzyme Q10 studies and effectsMitochondrial Function and PathologyBiotin and Related Studies

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

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Park, Isaac, Kim, Kwang-eun, Kim, Jeesoo, Kim, Ae-Kyeong, Bae, Subin, Jung, Minkyo, Choi, Jinhyuk, Mishra, Pratyush Kumar, Kim, Taek-Min, Kwak, Chulhwan, Kang, Myeong-Gyun, Yoo, Chang-Mo, Mun, Ji Young, Liu, Kwang-Hyeon, Lee, Kyu-Sun, Kim, Jong-Seo, Suh, Jae Myoung, Rhee, Hyun-Woo·2024·Nature Chemical Biology
DOI 10.1038/s41589-023-01452-wPMC PMC10830421

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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.

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Metadata

Authors
Park, I., Kim, K.-E., Kim, J., Kim, A.-K., Bae, S., Jung, M., Choi, J., Mishra, P. K., Kim, T.-M., Kwak, C., Kang, M.-G., Yoo, C.-M., Mun, J. Y., Liu, K.-H., Lee, K.-S., Kim, J.-S., Suh, J. M., & Rhee, H.-W.
Affiliations
  • Seoul National University (KR)
  • Korea Research Institute of Bioscience and Biotechnology (KR)
  • Kyungpook National University (KR)
  • Korea Brain Research Institute (KR)
  • Korea Advanced Institute of Science and Technology (KR)
Corresponding author
  • Kim, Jeesoo
  • Kim, Jong-Seo
  • Suh, Jae Myoung
  • Rhee, Hyun-Woo
ORCID
Venue
Nature Chemical Biology
Publisher
Springer Science and Business Media LLC
Published
2023-10-26
Volume
20
Issue
2
Pages
221-233
ISSN
  • 1552-4450 (ISSN-L)
  • 1552-4469
DOI
10.1038/s41589-023-01452-w
PMC
PMC10830421
OpenAlex
W4387965110
Cited by
39
References
5
Citations by year
2026: 12 · 2025: 14 · 2024: 8 · 2023: 3
FWCI
3.30
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Chemical Biology (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • Korea Brain Research Institute (BR-01-03)
  • National Research Foundation (2021R1A2C2007573, 2018R1A2A3075389, NRF-2019M3E5D3073104, NRF-2021R1A5A1033157)
  • Seoul National University (IBS-R008-D1)
  • Korea Health Industry Development Institute (HU20C0326)
  • Korea Research Institute of Bioscience and Biotechnology (KGM5392212)
  • National Research Foundation of Korea (NRF-2018R1A2A3075389, 2018R1A2A3075389, NRF-2022M3A9I2082294, NRF-2022M3E5E8081185, IBS-R008-D1, NRF-2019R1A2C3008463, NRF-2022R1C1C2004982, NRF-2021R1A2C2009336, 2022M3A9I2082294, NRF-2017R1A5A1015366, HU20C0326, NRF 2022R1A2B5B03001658, 23-BR-04-04, 2019M3E5D3073104, NRF-2019M3E5D3073104, NRF-2021R1A5A1033157, NRF-2022M3H9A2096199, 2019R1A2C2089484, 2021R1A5A1033157, 2017K1A1A2013124, NRF 2017K1A1A2013124, 2017R1A5A1015366)
  • Korea Advanced Institute of Science and Technology
  • Institute for Basic Science (IBS-R008-D1, R008-D1)
  • Ministry of Science and ICT, South Korea (2022M3A9I2082294, IBS-R008-D1, NRF‐2017R1A5A1015366, 21-BR-01-11, 2021R1A5A1033157, NRF-2021R1A5A1033157, NRF-2019M3E5D3073104, 23-BR-01-03)
  • Samsung Science and Technology Foundation (SSTF-BA2201-08)
  • Samsung
  • Korea Evaluation Institute of Industrial Technology
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Coenzyme Q10 studies and effects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Biotin and Related Studies
Keywords
coenzyme Q biosynthesis, mitochondrial matrix, NADPH oxidoreductase, ascorbate peroxidase, muscle respiration
MeSH terms
Animals, Carrier Proteins, Drosophila melanogaster, Mice, Transgenic, Mitochondria, Oxidoreductases, Ubiquinone, Proteome, Mitochondrial Proteins, Mice

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