Evaluation of the roles of apoptosis, autophagy, and mitophagy in the loss of plating efficiency induced by Bax expression in yeast.
We found recently that, in yeast cells, the heterologous expression of Bax induces a loss of plating efficiency different from that induced by acute stress because it is associated with the maintenance of plasma membrane integrity (Camougrand, N., Grelaud-Coq, A., Marza, E., Priault, M., Bessoule, J. J., and Manon, S. (2003) Mol. Microbiol. 47, 495-506). Bax effects were neither dependent on the presence of the yeast metacaspase Yca1p and the apoptosis-inducing factor homolog nor associated with the appearance of typical apoptotic markers such as metacaspase activation, annexin V binding, and DNA cleavage. Yeast cells expressing Bax instead displayed autophagic features, including increased accumulation of Atg8p, activation of vacuolar alkaline phosphatase, and the presence of autophagosomes and autophagic bodies. However, the inactivation of autophagy did not prevent and actually slightly accelerated Bax-induced loss of plating efficiency. On the other hand, Bax expression induced a fragmentation of the mitochondrial network, which retained, however, some level of organization in wild-type cells. However, when expressed in cells inactivated for the gene UTH1, previously shown to be involved in mitophagy, Bax induced a complete disorganization of the mitochondrial network. Interestingly, although mitochondrially targeted green fluorescent protein was slowly degraded in the wild-type strain, it remained unaffected in the mutant. Furthermore, the slow loss of plating efficiency in the mutant strain correlated with a loss of plasma membrane integrity. These data suggest that Bax-induced loss of growth capacity is associated with maintenance of plasma membrane integrity dependent on UTH1, suggesting that selective degradation of altered mitochondria is required for a regulated loss of growth capacity.
Kissová
Ingrid
I
UMR5095 CNRS/Université de Bordeaux 2, 1 Rue Camille Saint-Saëns, 33077 Bordeaux Cedex, France.
Plamondon
Louis-Thomas
LT
Brisson
Louise
L
Priault
Muriel
M
Renouf
Vincent
V
Schaeffer
Jacques
J
Camougrand
Nadine
N
Manon
Stéphen
S
D017209:Apoptosis; D001343:Autophagy; D020169:Caspases / Q000378:metabolism; D016923:Cell Death; D002462:Cell Membrane / Q000378:metabolism; D003470:Culture Media / Q000378:metabolism; D053938:DNA Fragmentation; D004318:Doxycycline / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D008954:Models, Biological; D010957:Plasmids / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
D003470:Culture Media; D029701:Saccharomyces cerevisiae Proteins; D051028:bcl-2-Associated X Protein; D049452:Green Fluorescent Proteins; D020169:Caspases; C456272:MCA1 protein, S cerevisiae; D004318:Doxycycline