Lipid Droplets and Peroxisomes: Key Players in Cellular Lipid Homeostasis or A Matter of Fat—Store ’em Up or Burn ’em Down

Abstract

Lipid droplets (LDs) and peroxisomes are central players in cellular lipid homeostasis: some of their main functions are to control the metabolic flux and availability of fatty acids (LDs and peroxisomes) as well as of sterols (LDs). Both fatty acids and sterols serve multiple functions in the cell—as membrane stabilizers affecting membrane fluidity, as crucial structural elements of membrane-forming phospholipids and sphingolipids, as protein modifiers and signaling molecules, and last but not least, as a rich carbon and energy source. In addition, peroxisomes harbor enzymes of the malic acid shunt, which is indispensable to regenerate oxaloacetate for gluconeogenesis, thus allowing yeast cells to generate sugars from fatty acids or nonfermentable carbon sources. Therefore, failure of LD and peroxisome biogenesis and function are likely to lead to deregulated lipid fluxes and disrupted energy homeostasis with detrimental consequences for the cell. These pathological consequences of LD and peroxisome failure have indeed sparked great biomedical interest in understanding the biogenesis of these organelles, their functional roles in lipid homeostasis, interaction with cellular metabolism and other organelles, as well as their regulation, turnover, and inheritance. These questions are particularly burning in view of the pandemic development of lipid-associated disorders worldwide.

Arabidopsis Lipins, PDAT1 Acyltransferase, and SDP1 Triacylglycerol Lipase Synergistically Direct Fatty Acids toward β-Oxidation, Thereby Maintaining Membrane Lipid Homeostasis

“…Under conditions of acute lipid overload, excess FAs are converted into biologically inert neutral lipids and packaged in specific subcellular organelles named lipid droplets (LDs) (Listenberger et al, 2003;Petschnigg et al, 2009;Kohlwein, 2010;Murphy, 2012;Kohlwein et al, 2013). In yeast (Saccharomyces cerevisiae), a critical enzyme involved in TAG synthesis (Han et al, 2006) and LD formation (Adeyo et al, 2011) is the Mg 2+ -dependent phosphatidic acid phosphohydrolase (Pah1), the homolog of the mammalian lipin protein family.…”

“…By contrast, increasing TAG synthesis by overexpression of ACYL-COA:DIACYLGLYCEROL ACYLTRANSFERASE1 (DGAT1) has been shown to cause a decrease in membrane phospholipid content in human cells (Bagnato and Igal, 2003). Interplay between TAG metabolism and membrane lipid synthesis is also evident from the observations that storage TAG hydrolysis can function as a source of lipid precursors for the synthesis of membrane phospholipids and signaling lipids in both yeast and mammals (Igal and Coleman, 1996;Kohlwein et al, 2013). Deficits in acylglycerol recycling from TAG to phospholipids are the likely cause of the neutral lipid storage disease in humans caused by mutations in COMPARATIVE GENE IDENTIFIER58 (CGI58) (Igal and Coleman, 1996).…”

Genome mining of fungal lipid-degrading enzymes for industrial applications

“…However, these ubiquitous lipases may turn to be important for supporting cell viability in the absence of carbon sources (van Zutphen et al, 2014). In yeast, deletion of genes encoding the lipid-dropletmobilized proteins, which included triacylglycerol lipase (patatin-domain-containing protein) and steryl ester hydrolase (abhydro_lipase-domain-containing protein), showed alterations in lipid droplet composition, size and number (Wagner et al, 2009;Kohlwein, 2010;Kohlwein et al 2013). According to enzyme topology in this study, the two elementary lipases behave as integral membrane proteins, which might be involved in the formation of lipid monolayers in addition to plasma membrane as suggested in previous reports (Athenstaedt et al, 1999;Athenstaedt & Daum, 2005).…”

“…Indeed, lipases play key roles not only in lipid degradation, but are also indirectly involved in lipid uptake and trafficking. Furthermore, the lipolytic enzymes contribute to cell homeostasis through lipid turnover and signal transduction processes (Müllner & Daum, 2004;Fickers et al, 2005a;Athenstaedt & Daum, 2006;Kohlwein, 2010;Kohlwein et al, 2013).…”

Hansenula polymorphaAat2p is targeted to peroxisomes via a novel Pex20p‐dependent pathway

“…Peroxisomes function in compartmentalizing a wide range of metabolic pathways, displaying a high degree of plasticity in their functions, depending on species and cell type 1. Some specific functions include glycolysis in trypanosomes and the production of penicillin in certain fungi while well‐conserved roles include the beta‐oxidation of fatty acids and hydrogen peroxide degradation 2.…”