Abstract
One of the basic building blocks of all life forms are lipids—biomolecules that dissolve in nonpolar organic solvents but not in water. Lipids have numerous structural, metabolic, and regulative functions in health and disease; thus, complex networks of enzymes coordinate the different compositions and functions of lipids with the physiology of the organism. One type of control on the activity of those enzymes is the conjugation of the Small Ubiquitin-like Modifier (SUMO) that in recent years has been identified as a critical regulator of many biological processes. In this review, I summarize the current knowledge about the role of SUMO in the regulation of lipid metabolism. In particular, I discuss (i) the role of SUMO in lipid metabolism of fungi and invertebrates; (ii) the function of SUMO as a regulator of lipid metabolism in mammals with emphasis on the two most well-characterized cases of SUMO regulation of lipid homeostasis. These include the effect of SUMO on the activity of two groups of master regulators of lipid metabolism—the Sterol Regulatory Element Binding Protein (SERBP) proteins and the family of nuclear receptors—and (iii) the role of SUMO as a regulator of lipid metabolism in arteriosclerosis, nonalcoholic fatty liver, cholestasis, and other lipid-related human diseases.
Highlights
2 of 20 2 of 20 in the maturation of Small Ubiquitin-like Modifier (SUMO) before its conjugation, the most common function of these proteases is ththee cmleaatvuaragteioonfofSSUUMMOOfbroefmoreitists tcaorngjeutga(dtieo-nS,UthMeOmyolasttioconm) minona fupnroctcieosns ocfotuhnesteerpacrotitnegaseSsUiMs tOhe ccolnejauvgaagteioonf.SUMO from its target in a process counteracting SUMO conjugation
YeIanstt—hethperRimeagruylamtioondeolf oLrigpaindiMsmetoafbofulinsgmi,btyheSUbuMdOdiinngEyuekaasrtySo.ticcerPervoistoiazeoparoteomic screens conduInctethdetopfirinmdaSrUy MmOodylealteodrgparnoitseminsoifnfvuinvgoi,bythiembmuudndoipnrgecyiepaitsattiSo.nc(eIrPe)viasniade mpraosste-sopmeicctroscmreeetrnys conducted to find SUMOylated proteins in vivo by immunoprecipitation (IP) and mass-spectrometry analysis (MS) have identified many proteins that are involved in lipid metabolism
Much of what we know about the role of SUMO in lipid metabolism comes from studies of mammals
Summary
A growing number of studies show the importance of Small Ubiquitin-like Modifier (SUMO) as a regulator of numerous cellular processes in health and disease [1,2]. In addition to the direct conjugation of SUMO to specific ERG proteins, SUMOylation is required for the nuclear localization of Multicopy suppressor of GAm1 (MGA2), a master regulator of fatty acid and sterol metabolism in S. cerevisiae [24]. In a ubc mutant background, the nuclear localization of the MGA2 transcription factor is impaired This finding suggests that transcriptional regulation is another mechanism by which SUMO may control lipid metabolism in S. cerevisiae. In C. elegans, several large-scale proteomic screens of IP and mass-spectrometry analysis have resulted in lists of candidate targets for direct SUMO conjugation [41,42] These candidates include, for example, the FAT-1 (omega-3 fatty acyl desaturase) and FAT-2 (Oleate/linoleate desaturase) proteins [41] as well as the FASN-1 (Fatty Acid SyNthase) enzyme [42]. Control of fatty acid and sterol metabolism by the SUMOylation of nuclear receptors in D. melanogaster is highly conserved in mammals as will be discussed below
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
