REVIEW article
Front. Physiol.
Sec. Mitochondrial Research
Role of mitophagy in breast cancer: mitophagy-apoptosis balance and reactive oxygen species play determining role
Provisionally accepted
- 1School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, Hong Kong, SAR China
- 2State Key Laboratory of Agrobiotechnology, The Chinese University of Hong Kong, Hong Kong SAR, Hong Kong, Hong Kong, SAR China
- 3Key Laboratory for Regenerative Medicine, Ministry of Education, The Chinese University of Hong Kong, Hong Kong SAR, Hong Kong, Hong Kong, SAR China
- 4Institute for Tissue Engineering and Regenerative Medicine, The Chinese University of Hong Kong, Hong Kong SAR, Hong Kong, Hong Kong, SAR China
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ABSTRACT This review aims to present a current overview of the role of mitophagy in breast cancer progression, especially from the point of view of when the cancer is in the untreated state or under chemotherapeutic treatment. We aim to explain the apparently contradictory results as reported in numerous studies on the differential role of mitophagy in breast cancer. We propose that different levels of reactive oxygen species (ROS), and the balance between mitophagy and apoptosis under different conditions are the major reasons to explain for the 'discrepancy'. If the cancer cells are untreated, a medium level of ROS promotes cancer progression. Mitophagy inhibition, which leave the dysfunctional mitochondria to generate more ROS, would therefore increase cancer progression. On the other hand, if the cancer cells are undergoing chemotherapeutic treatment, the excessively high level of ROS generated would stimulate both mitophagy and apoptosis, where mitophagy would inhibit apoptosis. In this case, inhibiting mitophagy would potentiate apoptosis and therefore enhance treatment effectiveness. The molecular mechanisms underlying the regulation between mitophagy and apoptosis are also discussed in this review. In summary, the review shall provide important insights for the role of mitophagy in breast cancer. It is proposed that the identification of the molecules involved in balancing mitophagy and apoptosis, and combined therapeutic strategies are the key areas for future exploration.
Keywords: Apoptosis reversal, BNIP3, mitophagy, PINK1, Reactive Oxygen Species
Received: 30 Sep 2025; Accepted: 10 Dec 2025.
Copyright: © 2025 Yiu, Chong, Yan and Tsang. 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: Suk Ying Tsang
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