Non-apoptotic caspase activation ensures the homeostasis of ovarian somatic stem cells

EMBO Rep. 2023 Jun 5;24(6):e51716. doi: 10.15252/embr.202051716. Epub 2023 Apr 11.

Abstract

Current evidence has associated caspase activation with the regulation of basic cellular functions without causing apoptosis. Malfunction of non-apoptotic caspase activities may contribute to specific neurological disorders, metabolic diseases, autoimmune conditions and cancers. However, our understanding of non-apoptotic caspase functions remains limited. Here, we show that non-apoptotic caspase activation prevents the intracellular accumulation of the Patched receptor in autophagosomes and the subsequent Patched-dependent induction of autophagy in Drosophila follicular stem cells. These events ultimately sustain Hedgehog signalling and the physiological properties of ovarian somatic stem cells and their progeny under moderate thermal stress. Importantly, our key findings are partially conserved in ovarian somatic cells of human origin. These observations attribute to caspases a pro-survival role under certain cellular conditions.

Keywords: Hedgehog signalling; autophagy; caspases; non-apoptotic; ovarian stem cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult Stem Cells* / metabolism
  • Animals
  • Apoptosis / physiology
  • Caspase 3 / metabolism
  • Caspase 8 / metabolism
  • Caspase 9 / metabolism
  • Caspases / genetics
  • Caspases / metabolism
  • Cell Death
  • Drosophila / metabolism
  • Hedgehog Proteins* / metabolism
  • Homeostasis
  • Humans

Substances

  • Hedgehog Proteins
  • Caspases
  • Caspase 3
  • Caspase 8
  • Caspase 9