Are sirtuin deacylase enzymes important modulators of mitochondrial energy metabolism?

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• 作者：Brenna Osborne^a ; ^{b.osborne@garvan.org.au" class="auth_mail} ; Gregory J. Cooney^a ; ^b ; ^{g.cooney@garvan.org.au" class="auth_mail} ; Nigel Turner^c ; ^{n.turner@unsw.edu.au" class="auth_mail}
• 关键词：AceCS2 ; acetyl-CoA synthetase 2 ; ADP ; adenosine diphosphate ; CPS1 ; carbamoyl phosphate synthetase 1 ; CPT1 ; carnitine palmitoyltransferase I ; CR ; calorie restriction ; FOXO3a ; forkhead box 03a ; GDH ; glutamate dehydrogenase ; HeLa ; human cervical carcinoma cells ; HIF-1伪 ; hypoxia inducible factor 1伪 ; HMGCS2 ; 3-hydroxy-3-methylglutaryl CoA synthase 2 ; IDH2 ; isocitrate dehydrogenase 2 ; LCAD ; long chain acyl-CoA dehydrogenase ; MCAD ; medium chain acyl coenzyme A dehydrogenase ; MCD ; malonyl-CoA decarbox
• 刊名：Biochimica et Biophysica Acta (BBA)/General Subjects
• 出版年：April, 2014
• 年：2014
• 卷：1840
• 期：4
• 页码：1295-1302
• 全文大小：660 K

文摘

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.