Disruption of endocytic pathway regulatory genes activates autophagy in C. elegans.

Autophagy and endocytic pathway are highly regulated catabolic processes. Both processes are crucial for cell growth, development, differentiation, disease and homeostasis and exhibit membrane rearrangement for their function. Autophagy and endocytic pathway represent branches of the lysosomal digestive system, autophagy being responsible for degradation of cytoplasmic components and endocytic pathway for degradation of exogenous substances. Here we report that autophagy is activated when endocytic pathway regulatory genes such as rab-5 and rabx-5 are disrupted. Defects in the ubiquitin binding domain of RABX-5 are critical in activating autophagy. We also observed that the elevated autophagy level does not contribute to lifespan extension of rabx-5 mutant. Our results suggest that autophagy may compensate for the endocytic pathway when regulatory genes for the endocytic pathway malfunction, providing a case of complementation between two functionally related cellular processes.