Decoding Mitophagy in Breast Cancer: Biological Mechanisms, Dual Roles, and Clinical Implications

Mitophagy is a selective form of autophagy, essential to maintain cellular homeostasis by removing damaged and dysfunctional mitochondria. Several lines of evidence suggest that defective mitophagy is associated with various diseases, including breast cancer. Disruption of mitochondrial quality control contributes to the production of reactive oxygen species, causing DNA damage and consequently tumorigenesis. Moreover, mitophagy contributes to the regulation of other mechanisms implicated in tumor progression, such as metabolic adaptability, maintenance of stem-like properties, and metabolic remodeling of immune cells. In breast cancer, the role of mitophagy is context-dependent, with evidence suggesting it can both suppress or promote breast cancer depending on tumor stage, tumor microenvironment, or molecular profile. For this reason, while targeting mitophagy represents a promising therapeutic strategy in breast cancer, additional investigation is required to clarify its complex role and how mitophagy modulation can be effectively translated into treatment strategies. This review aims to report on the main evidence on the role of mitophagy in breast cancer, exploring mitophagy-targeted approaches in order to potentially overcome drug resistance in breast cancer.