The N-Acetylcysteine-Insensitive Acetic Acid-Induced Yeast Programmed Cell Death Occurs Without Macroautophagy

Lucia      Antonacci; Nicoletta      Guaragnella; Masa      Zdralevic; Salvatore      Passarella; Ersilia      Marra; Sergio      Giannattasio

Abstract

Programmed cell death can occur through two separate pathways caused by treatment of Saccharomyces cerevisiae with acetic acid (AA-PCD), which differ from one another essentially with respect to their sensitivity to Nacetylcysteine (NAC) and to the role played by cytochrome c and metacaspase YCA1. Moreover, yeast can also undergo macroautophagy which occurs in NAC-insensitive manner. In order to gain some insight into the relationship between AA-PCD and macroautophagy use was made of WT and knock-out cells lacking YCA1 and/or cytochrome c. We show that i. macroautophagy is modulated by YCA1 and by cytochrome c in a negative and positive manner, respectively, ii. the NAC-insensitive AA-PCD and macroautophagy differ from one another and iii. NAC-insensitive AA-PCD pathway takes place essentially without macroautophagy, even if the shift of extracellular pH to acidic values required for AA-PCD to occur leads itself to increased or decreased macroautophagy in YCA1 or cytochrome c-lacking cells.

Keywords: Cytochrome c, macroautophagy, N-acetylcysteine, programmed cell death, Saccharomyces cerevisiae, YCA1, c-lacking cells, autophagic cell death, proteolytic activities, mitochondrial function