Did we miss something important? Rethinking the effects of autophagy and mitophagy on DNA damage repair and genomic stability

Abstract

Autophagy, a cellular recycling process, plays a key role in maintaining genomic stability and regulating DNA damage repair. However, recent studies have challenged this consensus, suggesting that upregulation of autophagy may induce DNA damage and contribute to genomic instability. Notably, several investigations have demonstrated that autophagy-mediated DNA damage can occur through mechanisms involving the production of reactive oxygen species (ROS). Despite these findings, many questions remain unresolved regarding the controversial DNA-damaging effects of autophagy and its potential role in promoting genomic instability and intratumoral heterogeneity. A more comprehensive understanding of the mechanisms and implications of “autophagy-mediated DNA damage” will offer crucial insights into the development and progression of various diseases from different perspectives. A deeper insight into autophagy mechanisms will also help identify potential adverse effects of autophagy-targeted interventions and clarify the molecular basis of side effects observed in various therapies in the future.

Keywords

Autophagy / BIRC5 / DNA damage repair / genomic instability / mitophagy / ROS

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