Drosophila Sirt2/mammalian SIRT3 deacetylates ATP synthase beta and regulates complex V activity
Authors
Rahman, MotiurNirala, Niraj K.
Singh, Alka
Zhu, Lihua Julie
Taguchi, Kaori
Bamba, Takeshi
Fukusaki, Eiichiro
Shaw, Leslie M.
Lambright, David G.
Acharya, Jairaj K.
Acharya, Usha R.
UMass Chan Affiliations
Department of Cancer BiologyProgram in Molecular Medicine
Program in Gene Function and Expression
Document Type
Journal ArticlePublication Date
2014-07-21
Metadata
Show full item recordAbstract
Adenosine triphosphate (ATP) synthase beta, the catalytic subunit of mitochondrial complex V, synthesizes ATP. We show that ATP synthase beta is deacetylated by a human nicotinamide adenine dinucleotide (NAD(+))-dependent protein deacetylase, sirtuin 3, and its Drosophila melanogaster homologue, dSirt2. dsirt2 mutant flies displayed increased acetylation of specific Lys residues in ATP synthase beta and decreased complex V activity. Overexpression of dSirt2 increased complex V activity. Substitution of Lys 259 and Lys 480 with Arg in human ATP synthase beta, mimicking deacetylation, increased complex V activity, whereas substitution with Gln, mimicking acetylation, decreased activity. Mass spectrometry and proteomic experiments from wild-type and dsirt2 mitochondria identified the Drosophila mitochondrial acetylome and revealed dSirt2 as an important regulator of mitochondrial energy metabolism. Additionally, we unravel a ceramide-NAD(+)-sirtuin axis wherein increased ceramide, a sphingolipid known to induce stress responses, resulted in depletion of NAD(+) and consequent decrease in sirtuin activity. These results provide insight into sirtuin-mediated regulation of complex V and reveal a novel link between ceramide and Drosophila acetylome.Source
Rahman M, Nirala NK, Singh A, Zhu LJ, Taguchi K, Bamba T, Fukusaki E, Shaw LM, Lambright DG, Acharya JK, Acharya UR. Drosophila Sirt2/mammalian SIRT3 deacetylates ATP synthase β and regulates complex V activity. J Cell Biol. 2014 Jul 21;206(2):289-305. doi: 10.1083/jcb.201404118. Link to article on publisher's siteDOI
10.1083/jcb.201404118Permanent Link to this Item
http://hdl.handle.net/20.500.14038/44040PubMed ID
25023514Related Resources
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This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
ae974a485f413a2113503eed53cd6c53
10.1083/jcb.201404118