Matai, Latika et al. (2015) International Worm Meeting "Oxidative quality control regulates response to ER stress through translation control."

Matai, Latika, Rajkumar, Asher, Sengupta, Shantanu, Maity, Shuvadeep, Mukhpadhyay, Arnab, Chakraborty, Kausik

[International Worm Meeting, 2015]

The Unfolded protein response is a signalling network that is triggered by the accumulation of misfolded proteins within the ER lumen, a condition termed as ER stress. Importantly, with progressing age, the ability of an organism to mount an effective response to ER stress declines significantly (Taylor and Dillin, 2013), the reason if resolved completely could have tremendous implications in aging research. In a comprehensive genetic screen to identify modulators of reductive stress-induced UPRER in S. cerevisiae, we found that oxidative quality control (OQC) genes modulate the cellular response to chronic reductive stress. Further studies in Caenorhabditis elegans revealed that ROS accumulation through pharmacological or genetic interventions results in non-canonical translation attenuation, blocking UPRER. Interestingly we find ROS accrual to be a potent reason for age related decline in iUPRER. We also show evidence that, ironically, the evolution of Perk-dependent translation attenuation system allows higher eukaryotes to bypass ROS-dependent non-canonical mode of translation attenuation by decreasing protein load in the ER.Keywords: ROS: Reactive oxygen species, iUPRER: induced UPRER.