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Effects of MOTS-c on the mitochondrial function of cells harboring 3243 A to G mutant mitochondrial DNA

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Abstract

Mitochondrial derived peptides (MDPs) are a class of peptide encoded in small open reading frames of mitochondrial DNA (mtDNA). MOTS-c, a recently discovered MDP, participates in retrograde signaling from the mitochondria to the nucleus to control cellular metabolism. Humanin, another MDP, has cytoprotective properties and enhances mitochondrial function. However, it has not yet been tested whether MOTS-c can affect mitochondrial function. We investigated the effect of exogenous and endogenous MOTS-c on mitochondrial function in a cybrid cell harboring 3243 A to G mutant mtDNA, which causes significant mitochondrial dysfunction. To test the effects of endogenous MOTS-c, the cybrid cell was transfected with a MOTS-c EGFP expression vector. Exogenous (synthetic) MOTS-c did not show a significant effect on the ATP content or the mRNA and protein levels of the mitochondrial complex in the mutant cybrid cells. Basal and stimulated mitochondrial respiration were also not affected by exogenous MOTS-c. The mutant cybrid cells transfected with the MOTS-c EGFP expression vector stably expressed MOTS-c, but ATP production and mRNA and protein levels of the mitochondrial complex were not affected. In contrast to other MDPs, MOTS-c does not improve mitochondrial dysfunction in cybrid cells with mutant mtDNA, which suggests the heterogeneous nature of MDPs.

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Acknowledgements

This research was supported by the Basic Science Research program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2017R1A2B4007166) and Seoul National University Hospital (0320160040). We thank Y. H. Wei from the National Yang-Ming University in Taiwan for providing the rho0 cell line. We also thank C. Lee from the University of Southern California for providing the MOTS-c-EGFP vector and anti-MOTS-c antibody.

Funding

This research was supported by the Basic Science Research program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2017R1A2B4007166) and Seoul National University Hospital (0320160040).

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Authors and Affiliations

  1. Department of Internal Medicine, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea

    Chang Ho Ahn, Eun Hye Choi, Byung Soo Kong & Young Min Cho

  2. Department of Translational Medicine, College of Medicine, Seoul National University, Seoul, Republic of Korea

    Chang Ho Ahn, Eun Hye Choi, Byung Soo Kong & Young Min Cho

  3. Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea

    Young Min Cho

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  1. Chang Ho Ahn
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  2. Eun Hye Choi
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Contributions

YMC and CHA designed the study. CHA, EHC and BSK conducted the experiments. CHA, EHC, BSK and YMC analyzed and interpreted the results. CHA and YMC wrote the manuscript.

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Correspondence to Young Min Cho.

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The authors declare that they have no conflict of interest.

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The protocol of this study was approved by the Institutional Review Board at Seoul National University Hospital (No. H-0406-127-001). All procedures performed in this study were in accordance with the ethical standards of the institutional committee and with the Declaration of Helsinki.

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Informed consent was obtained from all individual participants included in the study.

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Ahn, C.H., Choi, E.H., Kong, B.S. et al. Effects of MOTS-c on the mitochondrial function of cells harboring 3243 A to G mutant mitochondrial DNA. Mol Biol Rep 47, 4029–4035 (2020). https://doi.org/10.1007/s11033-020-05429-z

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  • DOI: https://doi.org/10.1007/s11033-020-05429-z

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