Acinus integrates AKT1 and subapoptotic caspase activities to regulate basal autophagy

Nilay Nandi, Lauren K. Tyra, Drew Stenesen, Helmut Krämer

Research output: Contribution to journalArticle

11 Citations (Scopus)

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 AcnS641,731D or the caspase-resistant AcnD527A, 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.

Original languageEnglish (US)
Pages (from-to)253-268
Number of pages16
JournalJournal of Cell Biology
Volume207
Issue number2
DOIs
StatePublished - 2014

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Autophagy
Caspases
Diptera
Drosophila Proteins
Caspase 1
Starvation
Proteolysis
Up-Regulation
Phosphorylation
Apoptosis
Mutation

ASJC Scopus subject areas

  • Cell Biology
  • Medicine(all)

Cite this

Acinus integrates AKT1 and subapoptotic caspase activities to regulate basal autophagy. / Nandi, Nilay; Tyra, Lauren K.; Stenesen, Drew; Krämer, Helmut.

In: Journal of Cell Biology, Vol. 207, No. 2, 2014, p. 253-268.

Research output: Contribution to journalArticle

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