Mitophagy-mediated immune evasion: Shared strategies of pathogens

Mitophagy selectively eliminates dysfunctional mitochondria, playing a pivotal role in mitochondrial quality control and cellular homeostasis. Emerging evidence reveals that certain pathogens exploit mitophagy to evade host immune defenses. Here, we provide novel insights into the regulatory mechanisms of mitophagy by integrating it with mitochondrial dynamics, and systematically review the mechanisms by which intracellular bacteria, viruses, and parasites utilize mitophagy to subvert host innate immunity. Notably, some pathogens dynamically regulate mitophagy at different infection stages to facilitate their survival, and the mitophagy show a positive correlation with mitochondrial fission/fragmentation. This review further summarizes four therapeutic strategies to counteract pathogen-induced immune evasion via mitophagy: 1) pharmacological modulation of mitophagy pathways; 2) mitochondria-targeted nanomaterials delivery systems; 3) mitochondria transplantation; 4) nanoengineered mitochondria. Moreover, two core mechanistic questions that remain to be addressed: (1) The mechanisms of time-dependent mitophagy-mediated immune evasion during infection, and (2) the mechanistic connection between mitochondrial dynamics and mitophagy. Future studies could employ label-free holographic tomography microscopy combined with artificial intelligence to visualize and quantify pathogen-induced subcellular alterations, enhancing our understanding of how mitophagy is manipulated, particularly through stage-specific regulation. These insights may open new avenues for treating infections resistant to conventional therapies.