Version 1
: Received: 30 July 2024 / Approved: 31 July 2024 / Online: 31 July 2024 (09:43:21 CEST)
How to cite:
Kitamura, H.; Fujimoto, M.; Hashimoto, M.; Yasui, H.; Inanami, O. USP2 Mitigates Reactive Oxygen Species–Induced Mitochondrial Damage via UCP2 Expression in Myoblasts. Preprints2024, 2024072531. https://doi.org/10.20944/preprints202407.2531.v1
Kitamura, H.; Fujimoto, M.; Hashimoto, M.; Yasui, H.; Inanami, O. USP2 Mitigates Reactive Oxygen Species–Induced Mitochondrial Damage via UCP2 Expression in Myoblasts. Preprints 2024, 2024072531. https://doi.org/10.20944/preprints202407.2531.v1
Kitamura, H.; Fujimoto, M.; Hashimoto, M.; Yasui, H.; Inanami, O. USP2 Mitigates Reactive Oxygen Species–Induced Mitochondrial Damage via UCP2 Expression in Myoblasts. Preprints2024, 2024072531. https://doi.org/10.20944/preprints202407.2531.v1
APA Style
Kitamura, H., Fujimoto, M., Hashimoto, M., Yasui, H., & Inanami, O. (2024). USP2 Mitigates Reactive Oxygen Species–Induced Mitochondrial Damage via UCP2 Expression in Myoblasts. Preprints. https://doi.org/10.20944/preprints202407.2531.v1
Chicago/Turabian Style
Kitamura, H., Hironobu Yasui and Osamu Inanami. 2024 "USP2 Mitigates Reactive Oxygen Species–Induced Mitochondrial Damage via UCP2 Expression in Myoblasts" Preprints. https://doi.org/10.20944/preprints202407.2531.v1
Abstract
Ubiquitin-specific protease 2 (USP2) maintains mitochondrial integrity in culture myoblasts. In this study, we investigated molecular mechanisms underlying the protective role of USP2 on mitochondria. Knockout (KO) of the Usp2 gene or chemical inhibition of USP2 induced robust accumulation of mitochondrial reactive oxygen species (ROS), accompanied by defects in mitochondrial membrane potential, in C2C12 myoblasts. ROS removal by N-acetyl-L-cysteine restored the mitochondrial dysfunction induced by USP2 deficiency. Comprehensive RT-qPCR screening and following protein analysis indicated that both genetic and chemical inhibition of USP2 elicited a decrease of uncoupling protein 2 (UCP2) at mRNA and protein levels. Accordingly, the introduction of a Ucp2-expressing construct effectively recovered mitochondrial membrane potentials, entailing an increment of the intracellular ATP level in Usp2KO C2C12 cells. In contrast, USP2 deficiency also decreased peroxisome proliferator-activated receptor coactivator 1 (PGC1 protein in C2C12 cells, while it upregulated Ppargc1a mRNA. Overexpression studies indicate that USP2 potentially stabilizes PGC1 in an isopeptidase-dependent manner. Given that PGC1 is an inducer of UCP2 in C2C12 cells, USP2 might ameliorate mitochondrial ROS by maintaining the PGC1–UCP2 axis in myoblasts.
Keywords
ubiquitin specific protease 2; myoblasts; mitochondria; ROS; uncoupling protein 2; PGC1alpha
Subject
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
