Elucidating the role of human obg like ATPase1 (hOLA1) in apoptosis

Abstract

hOLA1 is a purine nucleotide binding protein that belongs to the P-loop GTPase family. hOLA1 suppresses protein synthesis by limiting ternary complex formation thus promoting the integrated stress response (ISR). ISR determines cell fate by activating or inhibiting pro- and anti-apoptotic proteins depending on the type of the stress condition. ISR facilitates cell survival in response to mild stress and promotes apoptosis in response to chronic stress. Depletion of hOLA1 leads to increased cell survival and diminished ISR. This study investigates the role of hOLA1 in apoptosis. My hypothesis was that diminished ISR in hOLA1-depleted cells leads to upregulation of anti-apoptotic proteins thus inhibiting apoptosis. Indeed, this study shows that hOLA1 depletion upregulates anti-apoptotic proteins such as cIAP1, cIAP2, and Bcl-xL, thus inhibiting apoptosis. The inhibition of apoptosis was studied by assessing caspase activation, cleaved poly (ADP-ribose) polymerase (PARP) level, and measuring apoptosis by propidium iodide (PI) staining and flow cytometry.