Autophagy is the principal intracellular degradation pathway that helps maintain cell homeostasis by degrading harmful protein aggregates and damaged mitochondria. It is known that abnormalities in autophagy cause serious diseases such as neurodegenerative diseases and cancer. Thus, autophagy is a fundamental and essential phenomenon for living organisms, and knowing its mechanism is indispensable for developing disease treatment and prevention methods. The most significant feature of autophagy is the creation of a new double-membrane organelle called the autophagosome. However, the involvement of sphingolipids in the formation of autophagosomes is entirely unknown. Therefore, we investigated the involvement of ceramide kinase (CerK) in the formation of autophagosomes.
CerK is an enzyme that produces ceramide-1-phosphate (C1P) from the ceramide, “the central molecule in sphingolipid metabolism.” This study found that CerK knockout cells had lower basal autophagy levels than WT cells. In CerK-KO cells, the treatment with rapamycin or bafilomycin A1 delayed formation of autophagosomes compared to WT cells. Furthermore, the knockdown of CerK in WT cells resulted in a decrease in the number of autophagosomes. These results indicate that CerK is involved in the formation of autophagosomes.