, Volume 21, Issue 7, pp 866–872 | Cite as

The fungicide Mancozeb induces metacaspase-dependent apoptotic cell death in Saccharomyces cerevisiae BY4741

  • F. J. Scariot
  • L. M. Jahn
  • J. P. Maianti
  • A. P. L. Delamare
  • S. EcheverrigarayEmail author


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.


Dithiocarbamate Programmed cell death Yeast ROS Mitochondrial membrane potential 



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.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

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Supplementary material 1 (DOCX 1763 kb)
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Supplementary material 2 (DOCX 1501 kb)


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • F. J. Scariot
    • 1
  • L. M. Jahn
    • 1
  • J. P. Maianti
    • 2
  • A. P. L. Delamare
    • 1
  • S. Echeverrigaray
    • 1
    • 3
    Email author
  1. 1.Laboratory of Applied Microbiology, Institute of BiotechnologyUniversity of Caxias do SulCaxias do SulBrazil
  2. 2.Department of Chemistry and Chemical BiologyHarvard UniversityCambridgeUSA
  3. 3.Cytogene Diagnósticos Moleculares Ltda.LageadoBrazil

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