The role of selective autophagy in pathogen infection

Autophagy is a highly conserved physiological process of material degradation and recycling. According to the different pathways of degrading cargo, autophagy is classified into three types: Macroautophagy, microautophagy and chaperonemediated autophagy (CMA). Macroautophagy refers to the process in which cargos to be degraded are wrapped in doublemembrane autophagosome and transported to lysosomes for degradation. Microautophagy refers to the process in which lysosomal membrane invagination or protrusion wraps the cargo to be degraded and directly degrades it. Chaperonemediated autophagy refers to the process in which molecular chaperones restore intracellular proteins from the folded state to the unfolded state, and then transport them to lysosomes for degradation. Autophagy was previously defined as a nonselective process induced under starvation conditions. However, developments in autophagy-related research and in-depth studies have revealed that autophagy can be either a non-selective or selective process. Selective autophagy refers to the selective cellular degradation process that targets and degrades dysfunctional organelles, misfolded proteins, or invading pathogens. According to the different targets of degradation, selective autophagy is divided into mitophagy, endoplasmic reticulum autophagy (ER-phagy), proteasome autophagy (proteaphagy), ribosomal autophagy (ribophagy), lipophagy, nucleophagy, and xenophagy, and so on. Currently, mitophagy, ER-phagy, and xenophagy are hot research topics. Mitophagy is an autophagic process that selectively targets and degrades damaged or redundant mitochondria and is essential for mitochondrial quality control and maintenance of cell homeostasis. In recent years, accumulating studies have shown that some viruses or bacteria regulate the mitophagy process by various direct or indirect strategies, thereby weakening innate immune responses such as type I interferon response, apoptosis, and the activation of inflammasome to facilitate infection. Further, ER-phagy is a selective autophagic process that targets and degrades damaged endoplasmic reticulum fragments and plays essential roles in endoplasmic reticulum quality control and maintenance of cellular homeostasis. The on-going studies on ER-phagy mechanism are limited compared with those on mitophagy mechanism, but studies have reported that ER-phagy plays a vital role in the immune escape of pathogens. Xenophagy refers to the process in which eukaryotic cells recognize and degrade invading pathogens through selective autophagy. However, some studies have reported that some invading pathogens such as Mycobacterium tuberculosis and Salmonella inhibit xenophagy in host to achieve intracellular survival. Selective autophagy is a process that targets different cargo that is to be degraded and shares some crucial autophagy-related proteins. When multiple selective autophagy processes simultaneously occur, these processes compete for the shared proteins. However, studies on the crosstalk between different selective autophagy processes are limited. In summary, this article reviews the molecular mechanisms of mitophagy, ER-phagy, and xenophagy and their roles in pathogen infection to provide a reference for selective autophagy-related studies.