Uncovering the Genetic Foundation of Autophagic Cell Death in Yeast
Most plant organs have a finite lifespan before they begin to senesce. Although this is a natural part of life, it also reduces the lifespan of flowers, fruits, and tubers. Moreover, abiotic stress seems to accelerate this process so that plants rarely recover from even brief periods of drought or salt stress. Attempts have been made to delay or fully inhibit the onset of senescence by genetically manipulating the levels of the hormones that control it. Unfortunately, these hormones control a number of developmental processes, so although the plants show no sign of premature aging, they also show numerous morphological abnormalities. We believe that it might be possible to delay senescence just as effectively by altering "down-stream" processes (those controlled by these hormones) in a surgical fashion that has little impact on other pathways.
The process that we believe could be valuable for this end is called autophagy. Autophagy is known to protect cells from nutrient deprivation, including that that occurs during salt stress, yet paradoxically, also contributes to programmed cell death when plants are attacked by pathogens. Although autophagy has sometimes been described as if it was a single process, it is in fact is a family of processes carried out in similar ways, by a common set of proteins cooperating with different sets of auxiliary proteins that alter the choice of targets. We are attempting to discover new processes by challenging mutant yeast strains with novel stresses. We propose to identify autophagic pathways that alternatively protect cells from the deleterious effects of toxic metals like zinc, and from the toxic effects caused by protein aggregation such as that that is thought to occur during aging. Our
plan is to use the genetically advantageous organism, yeast, to identify these genes but once these genes have been identified there, it will be possible to look in the plant genome for equivalents that are responsible for the same effects. Yeast has proven to be an invaluable model for the discovery of genes associated with control of cell division, control of cell death, and responsible for repairing cellular damage. We fully expect, therefore, that the dissection of autophagic processes in yeast will prove equally enlightening for studies of autophagic processes in plants. Based on past experience, we also believe yeast can become a convenient test system for screening for chemicals able to target the identified genes so that researchers and farmers can suppress death or extend life as desired in our crops.