Mitophagy in pathogenesis and therapeutic implications for infection

Abstract Mitophagy, a critical selective autophagy pathway targeting dysfunctional mitochondria, is involved in cellular homeostasis and quality control under various stressors. During infection, invading pathogens cause mitochondrial abnormalities that trigger mitophagy. Most bacteria and viruses can exploit mitophagy as a pro-pathogenic process to escape host antiviral responses during infection. Emerging evidence suggests that restoring mitophagy is beneficial for mitigating excessive inflammation, such as in sepsis, whereas mitophagy blockade can activate host defense during bacterial and viral infections. Here we review current knowledge on the role of mitophagy in bacterial and viral infections and sepsis, focusing on the mechanisms by which pathogens evade mitophagy or influence pathogenesis through mitophagy during different types of infection. We also highlight the potential beneficial effects of mitophagy modulators, reagents and small molecules against sepsis-induced pathologies and infections. Progress in these areas will expand our knowledge on alleviating pathology, promoting antimicrobial immune responses and maintaining cellular homeostasis, ultimately providing potential preventive and therapeutic strategies against pathogenic infections and inflammation associated with dysregulated mitophagy.