Reactome | SIRT3 deacetylates Ac-K272,K290-FOXO3

SIRT3 deacetylates Ac-K272,K290-FOXO3

Stable Identifier

R-HSA-9841847

Type

Reaction [transition]

Species

Homo sapiens

Compartment

mitochondrial matrix

ReviewStatus

3/5

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In response to unfolded protein in the mitochondrial intermembrane space or the mitochondrial matrix, levels of SIRT3 mRNA increase and SIRT3 causes deacetylation of the transcription factor FOXO3. The increase in SIRT3 requires reactive oxygen species and the deacetylation may be indirect (Papa and Germain 2014); however, SIRT3 is observed to directly interact with FOXO3 in other situations: SIRT3 directly deacetylates FOXO3 in response to oxidative stress (Tseng et al. 2013) or hypoxia (Tseng et al. 2014). Additionally, the N-terminus of SIRT3 is cleaved during import into the matrix (Celestini et al. 2018) and imported SIRT3 forms a complex with FOXO3 in the mitochondrial matrix (Jacobs et al. 2008, Peserico et al. 2013).

Literature References

PubMed ID	Title	Journal	Year
24324009	SirT3 regulates the mitochondrial unfolded protein response Papa, L, Germain, D	Mol Cell Biol	2014
23665396	SIRT3 deacetylates FOXO3 to protect mitochondria against oxidative damage Tseng, AH, Shieh, SS, Wang, DL	Free Radic. Biol. Med.	2013
25162939	SIRT3 interactions with FOXO3 acetylation, phosphorylation and ubiquitinylation mediate endothelial cell responses to hypoxia Shieh, SS, Tseng, AH, Wang, DL, Wu, LH	Biochem J	2014