A primordial mover for sphingolipids

In people with Niemann Pick Type C disease (NP-C), a fatal neurodegenerative disorder, both sphingolipids and cholesterol accumulate in lysosomes, but controversy swirls around which of these metabolites causes the disease. On page 547, Malathi et al. present evidence that NPC1, the protein that is defective in most NP-C patients, may have evolved primarily to transport sphingolipids, as it can be replaced by a yeast version with only the sphingolipid functionality. The data favor the idea that sphingolipids are the offending metabolite in NP-C, and suggest that a redundant pathway for sphingolipid transport could be an attractive target for novel NP-C therapies.

Chinese hamster ovary cells lacking NPC1 exhibit aberrant sphingolipid and cholesterol accumulation. In the new work, the authors found that expressing NCR1, the yeast orthologue of NPC1, repairs all of the...