GLS2 and hepatocellular carcinoma: However, under ferroptosis (GSH/GPX4 decrease), there is a shift in GLS2 activity: GLS2 catalyzes more production of α-ketoglutarate (using glutamate) that in turn activates the TCA cycle and ETC, thereby increasing lipid ROS; accordingly, xenograft tumors with GLS2 overexpression exhibit reduced tumor size and lower GLS2 in vivo correlates with hepatocellular carcinoma development [172].