Divergent Roles of Autophagy in Virus Infection

Chiramel, Abhilash I.; Brady, Nathan R.; Bartenschlager, Ralf

In general, autophagy can be broadly classified as macroautophagy, microautophagy and chaperonemediated autophagy (CMA). All three pathways share the same mode of degradation via the lysosome, but are mechanistically distinct from each other [1] . Microautophagy, mainly characterized in yeast [2] , involves a direct engulfment of the cytoplasm at the lysosomal membrane, facilitated by protrusion of arm-like structures, and CMA specifically directs translocation of unfolded proteins with an inherent consensus motif (KFERQ) across the limiting membrane of the lysosome for degradation [1] . Furthermore, a crucial component for CMA is the lysosomal membrane receptor, lysosome-associated membrane protein (LAMP) type 2A [1] . In contrast to CMA, macroautophagy (called autophagy henceforth) involves sequestration of intact organelles (e.g., mitochondria) and portions of the cytosol via a membrane referred to as the phagophore or isolation membrane [3, 4] . This phagophore expands to form double-membrane vesicles, termed autophagosomes [3, 4] . Subsequently, autophagosomes mature by fusing with endosomes and/or lysosomes to form autolysosomes, where degradation of the internal contents occurs by resident lysosomal hydrolases [5] . The membrane source for the biogenesis of the phagophore is debatable; however, several recent studies have shown that the endoplasmic reticulum (ER), mitochondria and plasma membrane (PM) serve as source for the phagophore [6 8] .