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Citation
Nandi, N., Tyra, L.K., Stenesen, D., Krämer, H. (2014). Acinus integrates AKT1 and subapoptotic caspase activities to regulate basal autophagy.  J. Cell Biol. 207(2): 253--268.
FlyBase ID
FBrf0226558
Publication Type
Research paper
Abstract

How cellular stresses up-regulate autophagy is not fully understood. One potential regulator is the Drosophila melanogaster protein Acinus (Acn), which is necessary for autophagy induction and triggers excess autophagy when overexpressed. We show that cell type-specific regulation of Acn depends on proteolysis by the caspase Dcp-1. Basal Dcp-1 activity in developing photoreceptors is sufficient for this cleavage without a need for apoptosis to elevate caspase activity. On the other hand, Acn was stabilized by loss of Dcp-1 function or by the presence of a mutation in Acn that eliminates its conserved caspase cleavage site. Acn stability also was regulated by AKT1-mediated phosphorylation. Flies that expressed stabilized forms of Acn, either the phosphomimetic Acn(S641,731D) or the caspase-resistant Acn(D527A), exhibited enhanced basal autophagy. Physiologically, these flies showed improvements in processes known to be autophagy dependent, including increased starvation resistance, reduced Huntingtin-induced neurodegeneration, and prolonged life span. These data indicate that AKT1 and caspase-dependent regulation of Acn stability adjusts basal autophagy levels.

PubMed ID
PubMed Central ID
PMC4210446 (PMC) (EuropePMC)
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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    J. Cell Biol.
    Title
    Journal of Cell Biology
    Publication Year
    1966-
    ISBN/ISSN
    0021-9525
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    Human Disease Models (1)
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    Experimental Tools (3)
    Transgenic Constructs (30)