Yeast UPS1 deficiency leads to UVC radiation sensitivity and shortened lifespan.

ABSTRACT

UPS1/YLR193C of Saccharomyces cerevisiae (S. cerevisiae) encodes a mitochondrial intermembrane space protein. A previous study found that Ups1p is needed for normal mitochondrial morphology and that UPS1 deficiency disrupts the intramitochondrial transport of phosphatidic acid in yeast cells and leads to an altered unfolded protein response and mTORC1 signaling activation. In this paper, we first provide evidence showing that the UPS1 gene is involved in the UVC-induced DNA damage response and aging. We show that UPS1 deficiency leads to sensitivity to ultraviolet C (UVC) radiation and that this effect is accompanied by elevated DNA damage, increased intracellular ROS levels, abnormal mitochondrial respiratory function, an increased early apoptosis rate, and shortened replicative lifespan and chronological lifespan. Moreover, we show that overexpression of the DNA damage-induced checkpoint gene RAD9 effectively eliminates the senescence-related defects observed in the UPS1-deficient strain. Collectively, these results suggest a novel role for UPS1 in the UVC-induced DNA damage response and aging.