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

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In vivo mitochondrial matrix proteome profiling reveals RTN4IP1/OPA10 as an antioxidant NADPH oxidoreductase

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Park, Isaac, Kim, Kwang-eun, Kim, Jeesoo, Bae, Subin, Jung, Minkyo, Choi, Jinhyuk, Kwak, Chulhwan, Kang, Myeong-Gyun, Yoo, Chang-Mo, Mun, Ji Young, Liu, Kwang-Hyeon, Kim, Jong-Seo, Suh, Jae Myoung, Rhee, Hyun-Woo·2021·Nature Chemical Biology
DOI 10.1101/2021.10.14.464368PMC PMC10830421

Preprint — published as 10.1038/s41589-023-01452-w · Paper page

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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 expressing a mitochondrial matrix-targeted ascorbate peroxidase (MAX-Tg) to analyze tissue-specific matrix proteomes. Desthiobiotin-phenol labeling of muscle tissues from MAX-Tg mice allowed for efficient profiling of mitochondrial-localized proteins in these tissues. Comparative analysis of matrix proteomes from MAX-Tg muscle tissues revealed differential enrichment of mitochondrial proteins related to energy production in between different muscle groups. Reticulon 4 interacting protein 1 (RTN4IP1), also known as Optic Atrophy-10 (OPA10), was highly enriched in the cardiac and soleus muscles and was found to localize to the mitochondrial matrix via a strong mitochondrial targeting sequence at its N-terminus. Protein structure analysis revealed that RTN4IP1 is an NADPH oxidoreductase with structural homology to bacterial quinone oxidoreductase. Enzymatic activity assays, interactome analysis, and metabolite profiling confirmed a function for RTN4IP1 in coenzyme Q (CoQ) biosynthesis. Rtn4ip1 -knockout C2C12 cells had reduced CoQ9 levels, were vulnerable to oxidative stress, and had decreased oxygen consumption rates and ATP production. Collectively, RTN4IP1 is a mitochondrial antioxidant NADPH oxidoreductase supporting oxidative phosphorylation activity in muscle tissue.

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Metadata

Authors
Park, I., Kim, K.-E., Kim, J., Bae, S., Jung, M., Choi, J., Kwak, C., Kang, M.-G., Yoo, C.-M., Mun, J. Y., Liu, K.-H., Kim, J.-S., Suh, J. M., & Rhee, H.-W.
Affiliations
  • Seoul National University (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
openRxiv
Published
2021-10-14
Volume
20
Issue
2
Pages
221-233
ISSN
1552-4450 (ISSN-L)
DOI
10.1101/2021.10.14.464368
PMC
PMC10830421
OpenAlex
W4387965110
Cited by
39
References
1
Citations by year
2026: 12 · 2025: 14 · 2024: 8 · 2023: 3 · 2022: 2
FWCI
3.30
Type
journal article
Language
en
Open access
Licence
cc-by
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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