Beyond self-eating: The control of nonautophagic functions and signaling pathways by autophagy-related proteins

Cadwell, Ken; Debnath, Jayanta

Polymorphisms in a noncoding region of ATG5 is associated with SLE, a multiorgan autoimmune disease characterized by antinuclear antibodies, indicative of improper immune activation toward cellular contents (Harley et al., 2008) . ATG5 in B cells is required for autoantibody generation in the Lpr and Tlr7 transgenic mouse models of SLE (Weindel et al., 2015; Arnold et al., 2016) , consistent with the role of autophagy in supporting the secretory burden and organelle homeostasis in differentiated B cells (Conway et al., 2013a; Pengo et al., 2013; Chen et al., 2014 Chen et al., , 2015a . In contrast to this proposed role of autophagy in B cells that facilitates SLE pathogenesis, the genetic ablation of LAP-specific ATGs in phagocytic cells results in inefficient clearance of dead cells and their immunogenic contents, leading to a SLE-like disease in mice (Martinez et al., 2016) . Thus, it is possible that inhibiting autophagy may ameliorate, whereas inhibiting LAP may exacerbate disease. Developing drugs that can exclusively target classic autophagy without effecting autophagy-related processes, or vice versa, may be necessary to treat certain disorders.