FIGURE 1: Mitochondrial targeting of CERT induces Bax-dependent apoptosis. Ceramides are synthesized through N-acylation of long-chain bases (LCB) by ceramide synthases (CerS) on the cytosolic surface of the endoplasmic reticulum (ER). The bulk of newly synthesized ceramides are transferred to the Golgi by the ceramide transfer protein CERT for metabolic conversion into sphingomyelin by a Golgi-resident SM synthase (SMS). Expression of mitoCERT, a CERT variant in which the Golgi-targeting pleckstrin homology domain was replaced by an outer mitochondrial membrane anchor, triggers Bax-dependent apoptosis by diverting the biosynthetic flow of ceramides to mitochondria. Figure adapted from Dadsena et al. (2019), Nat Commun 10:1832. doi: 10.1038/s41467-019-09654-4