Yeast caspase 1, a possible antioxidant enzyme belonging to a mitochondrial originated antioxidation process

摘要

Caspases were regarded as enzymes to execute suicide. But now some caspases are found to have physiological functions. Yeast caspase 1 (Ycalp) is a metacaspase which brings apoptosis-like cell death in yeast Saccharomyces cerevisiae. But to the unicellular yeast cell, there is no advantage of committing apoptosis-like cell suicide. We presume that Ycalp have a role in the moment that cell is in an oxidation crisis. So we studied the effect of Ycalp to the yeast while cell is under severe oxidation stress. The results show that, formic acid treatment can induce a fast ROS burst both in wild type cells and YCA1 gene null cells of Saccharomyces cerevisiae. But during the ROS burst in log growth phase cells, which is observed with confocal microscope and analyzed with FACS, we found that knock out of ycal gene or inhibition of Ycalp activity makes the ROS in cytoplasmy reach a higher level and cause more cell death. With the aging of cells, ycal mutant shows a faster loss of mitochondrial membrane potential, which may be a result of more oxidative damage. We hypothesize that Yeast caspase 1 is a part of a mitochondrial originated and conservative antioxidant process, which is an adaptation of aerobic metabolism: more aspartic residue in protein surface is a consequence of protein oxidation, and during ROS burst, the aspartic enzyme activity of Ycalp looses the structure of oxidization protein and leads to quickly degradation of oxidized protein, which results in a faster scavenge of ROS. This hypothesis may be helpful to explain some phenotypes of yeast cell apoptosis, for example nucleus condensation, which may be part of this defensive antioxidant process.