TY - JOUR
T1 - The fungicide Mancozeb induces metacaspase-dependent apoptotic cell death in Saccharomyces cerevisiae BY4741
AU - Scariot, F. J.
AU - Jahn, L. M.
AU - Maianti, J. P.
AU - Delamare, A. P.L.
AU - Echeverrigaray, S.
N1 - Funding Information:
The authors acknowledge Cytogene Diagnósticos Moleculares Ltda. for access to flow cytometry equipment. F. J. Scariot thanks Coordenação de Aperfeiçoamento de Pessoal de Nivel Superior for fellowship support.
Publisher Copyright:
© 2016, Springer Science+Business Media New York.
PY - 2016/7/1
Y1 - 2016/7/1
N2 - Mancozeb (MZ), a mixture of ethylene-bis-dithiocarbamate manganese and zinc salts, is one of the most widely used fungicides in agriculture. Toxicologic studies in mammals and mammalian cells indicate that this fungicide can cause neurological and cytological disorders, putatively associated with pro-oxidant and apoptotic effects. Yeast adaptation to sub-inhibitory concentrations of MZ has been correlated with oxidative response, proteins degradation, and energy metabolism, and its main effect on yeast has been attributed to its high reactivity with thiol groups in proteins. Herein, we show that acute MZ treatments on aerobic exponentially growing yeast of wild type (BY4741) and deletion mutant strains, coupled with multiplex flow cytometry analysis, conclusively demonstrated that MZ displays the typical features of pro-oxidant activity on Saccharomyces, elevating mitochondrial ROS, and causing hyper-polarization of mitochondrial membranes leading to apoptosis. A drastic reduction of cellular viability associated with the maintenance of cell membrane integrity, as well as phosphatidyl serine externalization on yeast cells exposed to MZ, also supports an apoptotic mode of action. Moreover, abrogation of the apoptotic response in yca1 deficient mutants indicates that metacaspase-1 is involved in the programmed cell death mechanism induced by MZ in yeast.
AB - Mancozeb (MZ), a mixture of ethylene-bis-dithiocarbamate manganese and zinc salts, is one of the most widely used fungicides in agriculture. Toxicologic studies in mammals and mammalian cells indicate that this fungicide can cause neurological and cytological disorders, putatively associated with pro-oxidant and apoptotic effects. Yeast adaptation to sub-inhibitory concentrations of MZ has been correlated with oxidative response, proteins degradation, and energy metabolism, and its main effect on yeast has been attributed to its high reactivity with thiol groups in proteins. Herein, we show that acute MZ treatments on aerobic exponentially growing yeast of wild type (BY4741) and deletion mutant strains, coupled with multiplex flow cytometry analysis, conclusively demonstrated that MZ displays the typical features of pro-oxidant activity on Saccharomyces, elevating mitochondrial ROS, and causing hyper-polarization of mitochondrial membranes leading to apoptosis. A drastic reduction of cellular viability associated with the maintenance of cell membrane integrity, as well as phosphatidyl serine externalization on yeast cells exposed to MZ, also supports an apoptotic mode of action. Moreover, abrogation of the apoptotic response in yca1 deficient mutants indicates that metacaspase-1 is involved in the programmed cell death mechanism induced by MZ in yeast.
KW - Dithiocarbamate
KW - Mitochondrial membrane potential
KW - Programmed cell death
KW - ROS
KW - Yeast
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UR - http://www.scopus.com/inward/citedby.url?scp=84966601358&partnerID=8YFLogxK
U2 - 10.1007/s10495-016-1251-4
DO - 10.1007/s10495-016-1251-4
M3 - Article
C2 - 27160815
AN - SCOPUS:84966601358
SN - 1360-8185
VL - 21
SP - 866
EP - 872
JO - Apoptosis
JF - Apoptosis
IS - 7
ER -
