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

Abstract

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.

Mitochondrial factors with dual roles in death and survival

“…This idea is consistent with the observation that overexpression of human Bcl-2 improves survival of yeast lacking superoxide dismutase (Longo et al, 1997). Furthermore, human Bcl-2 and Bcl-xL can replace the anti-death function of yeast Fis1, and also inhibit yeast mitochondrial fragmentation following a death stimulus .…”

Bcl-2 family members inhibit oxidative stress-induced programmed cell death in Saccharomyces cerevisiae

“…Previous work by Longo et al [12] has shown that yeast cells harboring Bcl-2 have enhanced survival ability. Under stationery phase death conditions, yeast cells expressing Bcl-2 live considerably longer than wild-type strains.…”

“…S. cerevisiae is sensitive both to H 2 O 2 and to superoxide-generating agents [9][10][11]. Yeast deletion mutants of antioxidant genes such as catalase, superoxide dismutase, and cytochrome c peroxidase result in strains hypersensitive to lethal effects of oxidative stresses relative to isogenic wild-type cells [1,5,12]. Growth under anaerobic condition does not exhibit such sensitivity to these mutants.…”

“…Yeast cells can also be induced to die in an apoptotic-like manner by expression of Bax or treatment with cycloheximide, implying that yeast cell death is an active process, as it is in a number of cases in mammalian cells. In addition, aging in yeast also appears to be associated with apoptosis [26], and Bcl-2 can extend the life span of wild-type yeast and delay death in yeast mutants lacking superoxide dismutase [12]. A common theme through many of these studies is the accumulation of ROS.…”

Fasting vs dietary restriction in cellular protection and cancer treatment: from model organisms to patients

“…Fasting has been demonstrated to selectively protect normal cells and mice, but not cancerous cells against oxidants and common chemotherapeutic agents (Longo et al, 1997;Raffaghello et al, 2008). In cancer patients, preliminary data suggest that fasting is not only safe and feasible, but may also be effective in reducing common side-effects associated with chemotherapy (Safdie et al, 2009).…”