Ceramide accumulation induces mitophagy and impairs β-oxidation in PINK1 deficiency

著者: Melissa Vos, Marija Dulovic‐Mahlow, Frida Mandik, Lisa Frese, Yuliia Kanana, Sokhna Haissatou Diaw, Julia Depperschmidt, Claudia Böhm, Jonas Rohr, Thora Lohnau, Inke R. König, Christine Klein - Proceedings of the National Academy of Sciences, PNAS 2021 被引用: 89

Significance Ceramide accumulates in Parkinson’s disease–related PINK1 deficiency to initiate ceramide-mediated mitophagy as an alternative pathway to overcome defective PINK1-related mitophagy and the concomitant increased requirements for mitochondrial clearance. Increased ceramide levels negatively correlate with β-oxidation and thus decrease efficiency of the electron transport chain, further increasing the need for mitochondrial clearance. Interfering with this vicious cycle can constitute a novel therapeutic strategy as suggested by our data showing that a reduction of ceramide levels or stimulation of β-oxidation improve the PINK1 -mutant phenotypes.