Caspase involvement in autophagy

Abstract

Caspases are a family of cysteine proteases widely known as the principal mediators of the apoptotic cell death response, but considerably less so as the contributors to the regulation of pathways outside cellular demise. In regards to autophagy, the modulatory roles of caspases have only recently begun to be adequately described. In contrast to apoptosis, autophagy promotes cell survival by providing energy and nutrients through the lysosomal degradation of cytoplasmic constituents. Under basal conditions autophagy and apoptosis cross-regulate each other through an elaborate network of interconnections which also includes the interplay between autophagyrelated proteins (ATGs) and caspases. In this review we focus on the effects of this crosstalk at the cellular level, as we aim to concentrate the main observations from research conducted so far on the fine-tuning of autophagy by caspases. Several members of this protease-family have been found to directly interact with key ATGs involved in different tiers across the autophagic cascade. Therefore, we firstly outline the core mechanism of macroautophagy in brief. In an effort to emphasize the importance of the intricate cross-regulation of ATGs and caspases, we also present examples drawn from Drosophila and plant models regarding the contribution of autophagy to apoptotic cell death during normal development. Keywords and abbreviationsautophagy; macroautophagy; mammals; caspases; apoptosis; crosstalk; regulation AMBRA-1Activating-molecule-in-Beclin1-regulated-autophagy-1 AMPK AMP-activated-protein-kinase ATG Autophagy-related gene ATG14L ATG14-likeBcl-2 B-cell lymphoma 2 • Autophagy is implicated in many physiological and pathological processes, where apoptosis is also involved DISC Death-inducing signalling complex FADD Fas-associated protein with death domain Open Questions• Does control of autophagy by caspases represent a central or a supplementary mode of regulation of this pathway?• Is caspase activation required to control autophagy?• To what extent do caspases affect autophagy and how exactly their effects on the pathway vary across different contexts?4

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