REVIEW article
Front. Physiol.
Sec. Exercise Physiology
Volume 16 - 2025 | doi: 10.3389/fphys.2025.1664909
Mitophagy as a Therapeutic Target for Exercise-Induced Fatigue: Modulation by Natural Compounds and Mechanistic Insights
Provisionally accepted
Miao Yu1
Xiaohong Li1Yingxin Zhang2Wensi Zhang1Tianlong Wang1Jialin Wang3Junwei Shao3Lixin Zhang1Yiting Sun1
Xianglong Meng3Xiujuan Jiang1
Xianjun Liu1,3*- 1Jilin Engineering Normal University, Changchun, China
- 2University of Waterloo, Waterloo, Canada
- 3China-Japan Union Hospital of Jilin University, Changchun, China
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Exercise-induced fatigue is closely associated with mitochondrial dysfunction, and mitophagy plays a critical role in maintaining mitochondrial homeostasis by clearing damaged mitochondria and reducing oxidative stress. This review systematically summarizes current evidence on the regulatory mechanisms of mitophagy in exercise-induced fatigue, particularly through pathways such as PINK1/Parkin, BNIP3/Nix, FUNDC1, and AMPK, and examines how natural compounds including sulforaphane, Rhodiola crenulata, ginseng, modulate these pathways to alleviate fatigue. These findings suggest the presence of mitophagy threshold in different models and highlight its potential as a therapeutic target for fatigue management. Ultimately, this review proposes novel strategies for developing natural anti-fatigue agents based on mitophagy regulation, while underscoring the need for further mechanistic studies in diverse physiological and pathological settings.
Keywords: mitophagy, Exercise fatigue, natural compounds, therapeutic targets, Mitophagy pathways
Received: 13 Jul 2025; Accepted: 13 Oct 2025.
Copyright: © 2025 Yu, Li, Zhang, Zhang, Wang, Wang, Shao, Zhang, Sun, Meng, Jiang and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Xianjun Liu, liuxianjun@jlenu.edu.cn
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.