Listeria hijacks host cell mitophagy to evade killing through a novel mitophagy receptor

Abstract

Abstract Mitophagy, a selective form of autophagy, plays a critical role in eliminating damaged or excessive mitochondria during cell homeostasis or challenge to maintain the organelle quality and function. Listeria monocytogenes (L.m) is an intracellular pathogen of humans and animals, and an important and widely used model organism to study bacterial pathogenesis and host defense. It is still unknown if bacterial pathogens can induce host cell mitophagy. We made use of an L.m model system to show that intracellular bacterial pathogens induced host mitophagy in macrophages. Through a mitophagy inhibitor and a mitophagy promoter, we demonstrated that L.m-induced mitophagy provided a survival advantage of the bacterial pathogen. We further identified an LC3-interacting region (LIR)-containing protein as a novel mitophagy receptor for L.m-induced mitophagy. Consistent with the results of the mitophagy inhibitor, deficiency of the mitophagy receptor resulted in much reduced L.m titers both in macrophages in vitro and in mice in vivo. Thus our study discovers a previously unappreciated strategy by pathogens to hijack a host cellular homeostasis system for their survival. Mitophagy inhibitor or targeting mitophagy machinery may be useful for developing efficient therapeutic strategies against infections.