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Studying Copper Nanoparticle-Induced Programmed Cell Death in Bacteria
Published on: May 16, 2025
Copper and manganese induce yeast apoptosis via different pathways
1State Key Laboratory of Biomembrane and Membrane Biotechnology, Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing 100084, China.
Molecular Biology of the Cell
|September 21, 2007
Summary
Both copper and manganese induce apoptosis in yeast cells at toxic levels, with necrosis occurring at higher concentrations. Mitochondria and specific proteins mediate these metal-induced cell death pathways.
Area of Science:
- Cell Biology
- Toxicology
- Biochemistry
Background:
- Metal ions are crucial for cellular function but can also be toxic.
- The precise mechanisms underlying metal-induced cellular toxicity remain incompletely understood.
- Essential nutrients like copper (Cu) and manganese (Mn) can exhibit dual roles, being beneficial at low concentrations and toxic at higher levels.
Purpose of the Study:
- To investigate the apoptotic effects of copper and manganese in the yeast Saccharomyces cerevisiae.
- To elucidate the molecular pathways involved in copper- and manganese-induced apoptosis.
- To identify key cellular components and signaling molecules that mediate metal toxicity.
Main Methods:
- Utilized Saccharomyces cerevisiae as a model organism.
- Assessed apoptosis and necrosis induction by varying concentrations of copper and manganese.
- Employed mitochondria-defective yeast strains to evaluate mitochondrial involvement.
- Measured reactive oxygen species (ROS) production.
- Investigated the role of specific genes, including metacaspase Yca1p and cyclophilin D homolog Cpr3p, through genetic screening and mutant analysis.
Main Results:
- Both copper and manganese induced significant apoptosis in yeast cells at moderately toxic concentrations, with necrosis predominating at higher levels.
- Mitochondria-defective yeast showed reduced apoptosis and increased survival under metal stress, confirming mitochondrial involvement.
- Copper-induced toxicity was associated with high ROS generation, which was mitigated by superoxide dismutase 2 overexpression.
- Manganese-induced apoptosis, but not copper-induced apoptosis, involved the yeast metacaspase Yca1p.
- A genetic screen identified Cpr3p, a cyclophilin D homolog, as crucial for copper-induced apoptosis, with Cpr3p mutants resistant to copper-induced apoptosis.
Conclusions:
- Copper and manganese exhibit dose-dependent toxicity, inducing apoptosis and subsequently necrosis in yeast.
- Mitochondria play a central role in mediating both copper- and manganese-induced apoptosis.
- Reactive oxygen species are key mediators of copper toxicity, but not manganese toxicity.
- Distinct molecular pathways, involving Yca1p for manganese and Cpr3p for copper, are implicated in metal-induced apoptosis, offering insights into metal toxicity diseases.
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