UMMS Affiliation

Program in Gene Function and Expression; Program in Molecular Medicine; Program in Bioinformatics and Integrative Biology; Department of Cancer Biology

Date

7-21-2014

Document Type

Article

Disciplines

Biochemistry | Cell Biology | Cellular and Molecular Physiology | Genetics and Genomics

Abstract

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.

Rights and Permissions

Citation: 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 site

Comments

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/).

Related Resources

Link to Article in PubMed

 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.