摘要 : In a recent study, characterization of novel mechanisms that regulate lethal autophagy revealed that C_(18)-ceramide stress mediates LC3B-II-ceramide binding on mitochondrial membranes to target autophagosomes for mitophagy induct... 展开 In a recent study, characterization of novel mechanisms that regulate lethal autophagy revealed that C_(18)-ceramide stress mediates LC3B-II-ceramide binding on mitochondrial membranes to target autophagosomes for mitophagy induction and tumor suppression. Autophagy promotes cell survival during starvation or it can progress to cell death (lethal autophagy). However, the mechanisms by which autophagy promotes or inhibits cell survival are unclear. Ceramide is a bioactive sphingolipid that mediates cell death. Recently, mammalian ceramide synthases 1-6 (CERS1 to CERS6), which regulate the de novo generation of cerami-des with specific fatty acid chain lengths, have been discovered. For example, CERS1 and CERS6 preferentially generate C_(18)- and C_(16)-ceramide, respectively. Ceramides generated by CERS1 to CER6 have distinct biological roles. CERS1 and C_(18)-ceramide have emerged as tumor suppressors in preclinical and clinical studies. However, mechanisms of ceramide signaling in the regulation of lethal autophagy have been enigmatic. 收起