Sphingolipid homeostasis in the endoplasmic reticulum and beyond
#MMPMID23545423
Breslow DK
Cold Spring Harb Perspect Biol
2013[Apr]; 5
(4
): a013326
PMID23545423
show ga
Sphingolipids are a diverse group of lipids that have essential cellular roles as
structural components of membranes and as potent signaling molecules. In recent
years, a detailed picture has emerged of the basic biochemistry of
sphingolipids-from their initial synthesis in the endoplasmic reticulum (ER), to
their elaboration into complex glycosphingolipids, to their turnover and
degradation. However, our understanding of how sphingolipid metabolism is
regulated in response to metabolic demand and physiologic cues remains
incomplete. Here I discuss new insights into the mechanisms that ensure
sphingolipid homeostasis, with an emphasis on the ER as a critical regulatory
site in sphingolipid metabolism. In particular, Orm family proteins have recently
emerged as key ER-localized mediators of sphingolipid homeostasis. A detailed
understanding of how cells sense and control sphingolipid production promises to
provide key insights into membrane function in health and disease.
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