Rabbit Anti-SIRT5 monoclonal antibody, clone KK095-12

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. (C) 2013 Elsevier B.V. All rights reserved.

Trypanosoma cruzi and Leishmania spp. are protozoan pathogens responsible for Chagas disease and leishmaniasis, respectively. Current therapies rely only on a very small number of drugs, most of them are inadequate because of their severe host toxicity or drug-resistance phenomena. In order to find therapeutic alternatives, the identification of new biotargets is highly desired. In this study, homology modelling, docking and molecular dynamics simulations have been used to generate robust 3D models of NAD(+)-dependent deacetylases from Trypanosoma and Leishmania spp., known as SIR2rp3, whose structures have never been described before. Molecular docking of known inhibitors revealed strong analogies with the mitochondrial human SIRT5 in terms of binding mode and interaction strength. On the other hand, by extending the analysis to the channel rims, regions of difference between host and parasitic targets, useful for future selective drug design projects, were pointed out.