VCP relocalization limits mitochondrial activity, GSH depletion and ferroptosis during starvation in PC3 prostate cancer cells

• DOI: 10.1111/gtc.12872
• Publication Date: 2021-05-25T15:37:25Z
• Authors: Promise Ogor; Tomoki Yoshida; Masaaki Koike; Akira Kakizuka
• Keywords: Male; 2. Zero hunger; 0303 health sciences; Glutamine; Prostatic Neoplasms; Glutathione; Mitochondria; 3. Good health; Protein Transport; 03 medical and health sciences; Valosin Containing Protein; PC-3 Cells; Ferroptosis; Humans

Abstract During periods of crisis, cells must compensate to survive. To this end, may need alter the subcellular localization crucial proteins. Here, we show that during starvation, VCP, most abundant soluble ATPase, relocalizes and forms aggregate‐like structures at perinuclear regions in PC3 prostate cancer cells. This movement is associated with a lowered metabolic state, which mitochondrial activity ROS production are reduced. VCP appears explicitly sense glutamine levels, as removal from complete medium triggered relocalization its addition starvation media blunted relocalization. Cells cultured Gln(+) exhibited uniformly distributed cytoplasm (free VCP) underwent ferroptotic cell death, was decrease GSH levels. Moreover, inhibitor, CB‐5083, prevented death. Likewise, expression GFP‐fused proteins, irrespective ATPase activities, displayed free death starvation. These results indicate essential for maintenance function employ strategy self‐aggregation suppress order escape novel VCP‐mediated survival mechanism.