A UDP-glucose derivative is required for vacuolar autophagic cell death

Autophagy
Emilie TressePierre Golstein

Abstract

Autophagic cell death in Dictyostelium can be dissociated into a starvation-induced sensitization stage and a death induction stage. A UDP-glucose pyrophosphorylase (ugpB) mutant and a glycogen synthase (glcS) mutant shared the same abnormal phenotype. In vitro, upon starvation alone mutant cells showed altered contorted morphology, indicating that the mutations affected the pre-death sensitization stage. Upon induction of cell death, most of these mutant cells underwent death without vacuolization, distinct from either autophagic or necrotic cell death. Autophagy itself was not grossly altered as shown by conventional and electron microscopy. Exogenous glycogen or maltose could complement both ugpB(-) and glcS(-) mutations, leading back to autophagic cell death. The glcS(-) mutation could also be complemented by 2-deoxyglucose that cannot undergo glycolysis. In agreement with the in vitro data, upon development glcS(-) stalk cells died but most were not vacuolated. We conclude that a UDP-glucose derivative (such as glycogen or maltose) plays an essential energy-independent role in autophagic cell death.

Citations

Aug 9, 2008·American Journal of Respiratory Cell and Molecular Biology·Ralf H HubnerRonald G Crystal
Jan 10, 2009·Biochimica Et Biophysica Acta·Corinne GiustiPierre Golstein
Feb 2, 2010·Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology·Irina V Shemarova
Jan 6, 2017·Cell Death & Disease·M F LucianiP Golstein
May 1, 2017·The FEBS Journal·Pierre Golstein
Apr 9, 2010·Molecular Biology of the Cell·Corinne GiustiPierre Golstein
Oct 22, 2010·Autophagy·Michael DuszenkoPaul A M Michels

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