Human Bcl-2 Reverses Survival Defects in Yeast Lacking Superoxide Dismutase and Delays Death of Wild-Type Yeast

Longo, Valter D.; Ellerby, Lisa M.; Bredesen, Dale E.; Valentine, Joan S.; Gralla, Edith B.

doi:10.1083/jcb.137.7.1581

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Article| June 30 1997

Human Bcl-2 Reverses Survival Defects in Yeast Lacking Superoxide Dismutase and Delays Death of Wild-Type Yeast

Valter D. Longo,

Valter D. Longo

*Department of Chemistry and Biochemistry, University of California at Los Angeles, Los Angeles, California 90095-1569; ‡Program on Aging, The Burnham Institute, La Jolla, California 92037; and §Neuroscience Department, University of California at San Diego, La Jolla, California 92093

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Lisa M. Ellerby,

Lisa M. Ellerby

*Department of Chemistry and Biochemistry, University of California at Los Angeles, Los Angeles, California 90095-1569; ‡Program on Aging, The Burnham Institute, La Jolla, California 92037; and §Neuroscience Department, University of California at San Diego, La Jolla, California 92093

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Dale E. Bredesen,

Dale E. Bredesen

*Department of Chemistry and Biochemistry, University of California at Los Angeles, Los Angeles, California 90095-1569; ‡Program on Aging, The Burnham Institute, La Jolla, California 92037; and §Neuroscience Department, University of California at San Diego, La Jolla, California 92093

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Joan S. Valentine,

Joan S. Valentine

*Department of Chemistry and Biochemistry, University of California at Los Angeles, Los Angeles, California 90095-1569; ‡Program on Aging, The Burnham Institute, La Jolla, California 92037; and §Neuroscience Department, University of California at San Diego, La Jolla, California 92093

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Edith B. Gralla

*Department of Chemistry and Biochemistry, University of California at Los Angeles, Los Angeles, California 90095-1569; ‡Program on Aging, The Burnham Institute, La Jolla, California 92037; and §Neuroscience Department, University of California at San Diego, La Jolla, California 92093

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Author and Article Information

Valter D. Longo

*Department of Chemistry and Biochemistry, University of California at Los Angeles, Los Angeles, California 90095-1569; ‡Program on Aging, The Burnham Institute, La Jolla, California 92037; and §Neuroscience Department, University of California at San Diego, La Jolla, California 92093

Lisa M. Ellerby

*Department of Chemistry and Biochemistry, University of California at Los Angeles, Los Angeles, California 90095-1569; ‡Program on Aging, The Burnham Institute, La Jolla, California 92037; and §Neuroscience Department, University of California at San Diego, La Jolla, California 92093

Dale E. Bredesen

*Department of Chemistry and Biochemistry, University of California at Los Angeles, Los Angeles, California 90095-1569; ‡Program on Aging, The Burnham Institute, La Jolla, California 92037; and §Neuroscience Department, University of California at San Diego, La Jolla, California 92093

Joan S. Valentine

*Department of Chemistry and Biochemistry, University of California at Los Angeles, Los Angeles, California 90095-1569; ‡Program on Aging, The Burnham Institute, La Jolla, California 92037; and §Neuroscience Department, University of California at San Diego, La Jolla, California 92093

Edith B. Gralla

*Department of Chemistry and Biochemistry, University of California at Los Angeles, Los Angeles, California 90095-1569; ‡Program on Aging, The Burnham Institute, La Jolla, California 92037; and §Neuroscience Department, University of California at San Diego, La Jolla, California 92093

1. Abbreviations used in this paper: SDC, synthetic dextrose complete medium; SOD, superoxide dismutase; YPD, yeast extract/peptone/dextrose.

Please address all correspondence to E.B. Gralla, Department of Chemistry and Biochemistry, University of California at Los Angeles, Box 156905, Los Angeles, CA 90095-1569. Tel.: (310) 825-2807. Fax: (310) 206-7197. e-mail: [email protected]

Received: September 18 1996

Revision Received: February 27 1997

Online ISSN: 1540-8140

Print ISSN: 0021-9525

1997

J Cell Biol (1997) 137 (7): 1581–1588.

https://doi.org/10.1083/jcb.137.7.1581

We expressed the human anti-apoptotic protein, Bcl-2, in Saccharomyces cerevisiae to investigate its effects on antioxidant protection and stationary phase survival. Yeast lacking copper-zinc superoxide dismutase (sod1Δ) show a profound defect in entry into and survival during stationary phase even under conditions optimal for survival of wild-type strains (incubation in water after stationary phase is reached). Expression of Bcl-2 in the sod1Δ strain caused a large improvement in viability at entry into stationary phase, as well as increased resistance to 100% oxygen and increased catalase activity. In addition, Bcl-2 expression reduced mutation frequency in both wild-type and sod1Δ strains. In another set of experiments, wild-type yeast incubated in expired minimal medium instead of water lost viability quickly; expression of Bcl-2 significantly delayed this stationary phase death. Our results demonstrate that Bcl-2 has activities in yeast that are similar to activities it is known to possess in mammalian cells: (a) stimulation of antioxidant protection and (b) delay of processes leading to cell death.

1997

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