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2015 ; 290
(25
): 15371-15379
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Dihydroceramides: From Bit Players to Lead Actors
#MMPMID25947377
Siddique MM
; Li Y
; Chaurasia B
; Kaddai VA
; Summers SA
J Biol Chem
2015[Jun]; 290
(25
): 15371-15379
PMID25947377
show ga
Sphingolipid synthesis involves a highly conserved biosynthetic pathway that
produces fundamental precursors of complex sphingolipids. The final reaction
involves the insertion of a double bond into dihydroceramides to generate the
more abundant ceramides, which are converted to sphingomyelins and
glucosylceramides/gangliosides by the addition of polar head groups. Although
ceramides have long been known to mediate cellular stress responses, the
dihydroceramides that are transiently produced during de novo sphingolipid
synthesis were deemed inert. Evidence published in the last few years suggests
that these dihydroceramides accumulate to a far greater extent in tissues than
previously thought. Moreover, they have biological functions that are distinct
and non-overlapping with those of the more prevalent ceramides. Roles are being
uncovered in autophagy, hypoxia, and cellular proliferation, and the lipids are
now implicated in the etiology, treatment, and/or diagnosis of diabetes, cancer,
ischemia/reperfusion injury, and neurodegenerative diseases. This minireview
summarizes recent findings on this emerging class of bioactive lipids.
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