Yeast acetic acid‐induced programmed cell death can occur without cytochrome c release which requires metacaspase YCA1

Abstract

Edited by Vladimir SkulachevKeywords: Yeast Programmed cell death Cytochrome c release Caspase Hydrogen peroxide a b s t r a c tTo investigate the role of cytochrome c (cyt c) release in yeast acetic acid-induced programmed cell death (AA-PCD), wild type (wt) and cells lacking metacaspase (Dyca1), cytochrome c (Dcyc1,7) and both (Dcyc1,7Dyca1) were compared for AA-PCD occurrence, hydrogen peroxide (H 2 O 2 ) production and caspase activity. AA-PCD occurs in Dcyc1,7 and Dcyc1,7Dyca1 cells slower than in wt, but similar to that in Dyca1 cells, in which no cytochrome c release occurs. Both H 2 O 2 production and caspase activation occur in these cells with early and extra-activation in Dcyc1,7 cells. We conclude that alternative death pathways can be activated in yeast AA-PCD, one dependent on cyt c release, which requires YCA1, and the other(s) independent on it.

Proteome and metabolome profiling of wild-type and YCA1 -knock-out yeast cells during acetic acid-induced programmed cell death

“…To compare the proteomic and metabolomic alterations caused by acetic acid treatment of either WT or yca1 cells, all analyses were carried out using either cells treated with acetic acid for 150 min, when the maximum or no release of cyt c, respectively, occurs [15,24], or cells before acetic acid treatment as control.…”

Crystal Structure of the Yeast Metacaspase Yca1

“…Specifically, Yca1 is classified as a type I metacaspase (11), with a characteristic N-terminal prodomain that is thought to be cleaved off upon activation. Although yeast is a single cell eukaryote, it is widely believed to undergo programmed cell death, or apoptosis, in response to detrimental environmental cues (6,(12)(13)(14)(15). Consequently, early skepticism on yeast apoptosis has now been replaced by systematic investigation on the genetic and biochemical pathways that control the onset of apoptosis in yeast.…”

“…Consequently, early skepticism on yeast apoptosis has now been replaced by systematic investigation on the genetic and biochemical pathways that control the onset of apoptosis in yeast. Yca1 appears to be a positive regulator of apoptosis upon stress induction by hydrogen peroxide, acetic acid, and toxin (6,(12)(13)(14)(15). Nuclear localization of poly(Q) expansions in S. cerevisiae was abolished in⌬yca1-null mutant strain, blocking apoptosis (16).…”

Metacaspases

“…17 Furthermore, metacaspase involvement in the yeast cell death models was investigated after in vivo staining for caspase activity by flow cytometry with FITC-labeled VAD-fmk (FITC-VAD-fmk). 17,[41][42][43][44] Likewise, in the fungus C. albicans, it was suggested that the antifungal compound Plagiochin E activated metacaspases based on the appearance of FITC-VAD-fmk labeled cells. 45 In the phytoplankton Chlamydomonas reinhardtii and other marine species, such as the diatom Thalassiosira pseudonana and the unicellular coccolithore Emiliania huxlei, increased caspase-like activity was correlated with increased accumulation of metacaspase mRNA and protein, thereby providing indirect evidence that metacaspases had caspase-like activity.…”