Sphingolipid metabolism - an ambiguous regulator of autophagy in the brain

In mammals, the brain exhibits the highest lipid content in the body next to adipose tissue. Complex sphingolipids are characteristic compounds of neuronal membranes. Vital neural functions including information flux and transduction occur along these membranes. It is therefore not surprising that neuronal function and survival is dependent on the metabolism of these lipids. Autophagy is a critical factor for the survival of post-mitotic neurons. On the one hand, it fulfils homeostatic and waste-recycling functions and on the other hand, it constitutes an effective strategy to eliminate harmful proteins that cause neuronal death. A growing number of experimental data indicate that several sphingolipids as well as enzymes catalyzing their metabolic transformations efficiently but very differently affect neuronal autophagy and hence survival. This review attempts to elucidate the roles and mechanisms of sphingolipid metabolism with regard to the regulation of autophagy and its consequences for brain physiology and pathology.