TY - JOUR

T1 - Are sirtuin deacylase enzymes important modulators of mitochondrial energy metabolism?

AU - Osborne, Brenna

AU - Cooney, Gregory J.

AU - Turner, Nigel

N1 - Funding Information: Work in the laboratories of the authors is supported by funding from the National Health and Medical Research Council of Australia (NHMRC) , the Australian Research Council and the Diabetes Australia Research Trust . BO is supported by a PhD scholarship and GJC by a research fellowship from the NHMRC. NT is supported by an ARC Future Fellowship .

PY - 2014/4

Y1 - 2014/4

N2 - Background In recent years, reversible lysine acylation of proteins has emerged as a major post-translational modification across the cell, and importantly has been shown to regulate many proteins in mitochondria. One key family of deacylase enzymes is the sirtuins, of which SIRT3, SIRT4, and SIRT5 are localised to the mitochondria and regulate acyl modifications in this organelle. Scope of review In this review we discuss the emerging role of lysine acylation in the mitochondrion and summarise the evidence that proposes mitochondrial sirtuins are important players in the modulation of mitochondrial energy metabolism in response to external nutrient cues, via their action as lysine deacylases. We also highlight some key areas of mitochondrial sirtuin biology where future research efforts are required. Major conclusions Lysine deacetylation appears to play some role in regulating mitochondrial metabolism. Recent discoveries of new enzymatic capabilities of mitochondrial sirtuins, including desuccinylation and demalonylation activities, as well as an increasing list of novel protein substrates have identified many new questions regarding the role of mitochondrial sirtuins in the regulation of energy metabolism. General significance Dynamic changes in the regulation of mitochondrial metabolism may have far-reaching consequences for many diseases, and despite promising initial findings in knockout animals and cell models, the role of the mitochondrial sirtuins requires further exploration in this context. This article is part of a Special Issue entitled Frontiers of mitochondrial research.

AB - Background In recent years, reversible lysine acylation of proteins has emerged as a major post-translational modification across the cell, and importantly has been shown to regulate many proteins in mitochondria. One key family of deacylase enzymes is the sirtuins, of which SIRT3, SIRT4, and SIRT5 are localised to the mitochondria and regulate acyl modifications in this organelle. Scope of review In this review we discuss the emerging role of lysine acylation in the mitochondrion and summarise the evidence that proposes mitochondrial sirtuins are important players in the modulation of mitochondrial energy metabolism in response to external nutrient cues, via their action as lysine deacylases. We also highlight some key areas of mitochondrial sirtuin biology where future research efforts are required. Major conclusions Lysine deacetylation appears to play some role in regulating mitochondrial metabolism. Recent discoveries of new enzymatic capabilities of mitochondrial sirtuins, including desuccinylation and demalonylation activities, as well as an increasing list of novel protein substrates have identified many new questions regarding the role of mitochondrial sirtuins in the regulation of energy metabolism. General significance Dynamic changes in the regulation of mitochondrial metabolism may have far-reaching consequences for many diseases, and despite promising initial findings in knockout animals and cell models, the role of the mitochondrial sirtuins requires further exploration in this context. This article is part of a Special Issue entitled Frontiers of mitochondrial research.

KW - Lysine acylation

KW - Mitochondrial metabolism

KW - Sirtuin

UR - http://www.scopus.com/inward/record.url?scp=84895522697&partnerID=8YFLogxK

U2 - 10.1016/j.bbagen.2013.08.016

DO - 10.1016/j.bbagen.2013.08.016

M3 - Review

C2 - 23994496

AN - SCOPUS:84895522697

VL - 1840

SP - 1295

EP - 1302

JO - B B A - General Subjects

JF - B B A - General Subjects

SN - 0304-4165

IS - 4

ER -