Identification of autophagy genes participating in zinc-induced necrotic cell death in Saccharomyces cerevisiae

Slawomir A Dziedzic; Allan B Caplan

doi:10.4161/auto.7.5.14872

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Identification of autophagy genes participating in zinc-induced necrotic cell death in Saccharomyces cerevisiae

Journal article

Open access

Peer reviewed

Identification of autophagy genes participating in zinc-induced necrotic cell death in Saccharomyces cerevisiae

Slawomir A Dziedzic and Allan B Caplan

Autophagy, Vol.7(5), pp.490-500

05/2011

DOI: https://doi.org/10.4161/auto.7.5.14872

Handle:

https://hdl.handle.net/2376/109912

PMCID: PMC3127211

PMID: 21317551

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Abstract

Microtubule-Associated Proteins - genetics

Apoptosis - drug effects

Microtubule-Associated Proteins - metabolism

Saccharomyces cerevisiae - genetics

Cell Survival - genetics

Apoptosis - genetics

Saccharomyces cerevisiae - drug effects

Green Fluorescent Proteins - genetics

Protein Transport - drug effects

Autophagy - drug effects

Cell Death - genetics

Time Factors

Cloning, Molecular

Saccharomyces cerevisiae Proteins - isolation & purification

Autophagy - genetics

Cell Death - drug effects

Organisms, Genetically Modified

Cell Survival - drug effects

Green Fluorescent Proteins - metabolism

Saccharomyces cerevisiae - physiology

Saccharomyces cerevisiae Proteins - genetics

Protein Transport - genetics

Necrosis - chemically induced

Autophagy-Related Protein 8 Family

Saccharomyces cerevisiae Proteins - metabolism

Zinc - toxicity

Cell Proliferation - drug effects

Necrosis - genetics

Apoptosis - physiology

Saccharomyces cerevisiae - growth & development

Eukaryotes use a common set of genes to perform two mechanistically similar autophagic processes. Bulk autophagy harvests proteins nonselectively and reuses their constitutents when nutrients are scarce. In contrast, different forms of selective autophagy target protein aggregates or damaged organelles that threaten to interfere with growth. Yeast uses one form of selective autophagy, called cytoplasm-to-vacuole targeting (Cvt), to engulf two vacuolar enzymes in Cvt vesicles ("CVT-somes") within which they are transported to vacuoles for maturation. While both are dispensable normally, bulk and selective autophagy help sustain life under stressful conditions. Consistent with this view, knocking out several genes participating in Cvt and specialized autophagic pathways heightened the sensitivity of Saccharomyces cerevisiae to inhibitory levels of Zn(2+). The loss of other autophagic genes, and genes responsible for apoptotic cell death, had no such effect. Unexpectedly, the loss of members of a third set of autophagy genes heightened cellular resistance to zinc as if they encoded proteins that actively contributed to zinc-induced cell death. Further studies showed that both sensitive and resistant strains accumulated similar amounts of H2O2 during zinc treatments, but that more sensitive strains showed signs of necrosis sooner. Although zinc lethality depended on autophagic proteins, studies with several reporter genes failed to reveal increased autophagic activity. In fact, microscopy analysis indicated that Zn(2+) partially inhibited fusion of Cvt vesicles with vacuoles. Further studies into how the loss of autophagic processes suppressed necrosis in yeast might reveal whether a similar process could occur in plants and animals.

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Title: Identification of autophagy genes participating in zinc-induced necrotic cell death in Saccharomyces cerevisiae
Creators: Slawomir A Dziedzic - Department of Microbiology, Molecular Biology, and Biochemistry, University of Idaho, Moscow, ID, USA
Allan B Caplan
Publication Details: Autophagy, Vol.7(5), pp.490-500
Academic Unit: UNKNOWN
Publisher: United States
Grant note: P20 RR016448 / NCRR NIH HHS
Identifiers: 99900547247501842
Language: English
Resource Type: Journal article