2016
DOI: 10.1074/jbc.m115.668228
|View full text |Cite
|
Sign up to set email alerts
|

SIRT3 Deacetylates Ceramide Synthases

Abstract: Experimental evidence supports the role of mitochondrial ceramide accumulation as a cause of mitochondrial dysfunction and brain injury after stroke. Herein, we report that SIRT3 regulates mitochondrial ceramide biosynthesis via deacetylation of ceramide synthase (CerS) 1, 2, and 6. Reciprocal immunoprecipitation experiments revealed that CerS1, CerS2, and CerS6, but not CerS4, are associated with SIRT3 in cerebral mitochondria. Furthermore, CerS1, -2, and -6 are hyperacetylated in the mitochondria of SIRT3-nu… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
1
1
1
1

Citation Types

1
31
0

Year Published

2017
2017
2022
2022

Publication Types

Select...
7
1

Relationship

0
8

Authors

Journals

citations
Cited by 70 publications
(35 citation statements)
references
References 85 publications
(126 reference statements)
1
31
0
Order By: Relevance
“…The presence of six tightly regulated and interdependent ceramide synthases plus their splice variants assures the necessary variation in synthesized ceramides [ 30 ]. CerSs are known to undergo phosphorylation, acetylation, N -glycosylation, and ubiquitination, implying tight (but still poorly understood) regulation [ 30 , 31 ].
Fig.
…”
Section: Sphingolipid Biosynthesis and Signalingmentioning
confidence: 99%
“…The presence of six tightly regulated and interdependent ceramide synthases plus their splice variants assures the necessary variation in synthesized ceramides [ 30 ]. CerSs are known to undergo phosphorylation, acetylation, N -glycosylation, and ubiquitination, implying tight (but still poorly understood) regulation [ 30 , 31 ].
Fig.
…”
Section: Sphingolipid Biosynthesis and Signalingmentioning
confidence: 99%
“…Binding of CERS6 to Fas persisted with C199V mutation, suggesting that C199 is not critical for CERS6 binding. BCL2L13 and SIRT3 are two proteins reported to be interacting with CERS6, where the former is shown to inhibit the activity of CERS6 44 , while the latter deacetylates CERS6 to cause an increase in its activity 45 . These interactions affect the activity of CERS6, but there are no reports showing that CERS6 affects the function of other proteins.…”
Section: Discussionmentioning
confidence: 99%
“…Clearly, the role of sirtuins in modulating gut microbiome-derived butyrate will modulate ceramide levels and effects in AD. This requires future investigation as some data indicates that under conditions of ischaemia-reperfusion, SIRT3 deacetylates ceramide synthase, leading to an increase in ceramide synthesis [92]. The interactions of the sirtuins with the regulation of ceramide at different sites will be important to determine…”
Section: Butyrate and Ceramidementioning
confidence: 99%
“…As noted, ceramide is damaging to mitochondria via a number of mechanisms, including decreasing mitochondrial Complex III, PDC and OXPHOS [92]. Recent work shows all factors and enzymes of the melatonergic pathway to be expressed in mitochondria [64], including AANAT, acetylserotonin methyltransferase (ASMT), 14-3-3 and acetyl-CoA, reviewed in [8].…”
Section: Gut Permeabilitymentioning
confidence: 99%
See 1 more Smart Citation