TRIM2: a double-edged sword preventing apoptosis

TRIM2 belongs to the TRIM-NHL class of ubiquitin E3-ligases and inhibits apoptosis by a dual function. Liao et al. reported in the recent issue that under glutamine deprivation, TRIM2 transcription is activated by ATF4 to increase the uptake of long fatty acids into mitochondria. Here, TRIM2 acts as a direct activator of CPT1 independent of its E3 ubiquitin ligase activity and prevents apoptosis otherwise triggered by starvation. On the contrary, TRIM E3-ubiquitin ligase has been described to ubiquitinate and thus target proapoptotic BIM for its degradation in the proteasome. Thus, TRIM2 inhibits apoptosis classically via its ligase activity but also independent of this stimulating energy metabolism.