Cp1/cathepsin L is required for autolysosomal clearance in Drosophila.

Cp1/cathepsin L is required for autolysosomal clearance in Drosophila.
Autophagy. 2020 Oct 28;:1-16
Authors: Xu T, Nicolson S, Sandow JJ, Dayan S, Jiang X, Manning JA, Webb AI, Kumar S, Denton D
Abstract
Macroautophagy/autophagy is a highly conserved lysosomal degradative pathway important for maintaining cellular homeostasis. Much of our current knowledge of autophagy is focused on the initiation steps in this process. Recently, an understanding of later steps, particularly lysosomal fusion leading to autolysosome formation and the subsequent role of lysosomal enzymes in degradation and recycling, is becoming evident. Autophagy can function in both cell survival and cell death, however, the mechanisms that distinguish adaptive/survival autophagy from autophagy-dependent cell death remain to be established. Here, using proteomic analysis of Drosophila larval midguts during degradation, we identify a group of proteins with peptidase activity, suggesting a role in autophagy-dependent cell death. We show that Cp1/cathepsin L-deficient larval midgut cells accumulate aberrant autophagic vesicles due to a block in autophagic flux, yet later stages of midgut degradation are not compromised. The accumulation of large aberrant autolysosomes in the absence of Cp1 appears to be the consequence of decreased degradative capacity as they contain undigested cytoplasmic material, rather than a defect in autophagosome-lysosome fusion. Finally, we fin...

Source: Autophagy - October 28, 2020 Category: Cytology Authors: Xu T, Nicolson S, Sandow JJ, Dayan S, Jiang X, Manning JA, Webb AI, Kumar S, Denton D Tags: Autophagy Source Type: research