The α/β Hydrolase CGI-58 and Peroxisomal Transport Protein PXA1 Coregulate Lipid Homeostasis and Signaling in Arabidopsis  

Abstract

COMPARATIVE GENE ) is a key regulator of lipid metabolism and signaling in mammals, but its underlying mechanisms are unclear. Disruption of CGI-58 in either mammals or plants results in a significant increase in triacylglycerol (TAG), suggesting that CGI-58 activity is evolutionarily conserved. However, plants lack proteins that are important for CGI-58 activity in mammals. Here, we demonstrate that CGI-58 functions by interacting with the PEROXISOMAL ABC-TRANSPORTER1 (PXA1), a protein that transports a variety of substrates into peroxisomes for their subsequent metabolism by b-oxidation, including fatty acids and lipophilic hormone precursors of the jasmonate and auxin biosynthetic pathways. We also show that mutant cgi-58 plants display changes in jasmonate biosynthesis, auxin signaling, and lipid metabolism consistent with reduced PXA1 activity in planta and that, based on the double mutant cgi-58 pxa1, PXA1 is epistatic to CGI-58 in all of these processes. However, CGI-58 was not required for the PXA1-dependent breakdown of TAG in germinated seeds. Collectively, the results reveal that CGI-58 positively regulates many aspects of PXA1 activity in plants and that these two proteins function to coregulate lipid metabolism and signaling, particularly in nonseed vegetative tissues. Similarities and differences of CGI-58 activity in plants versus animals are discussed.

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

“…To date, although most of the enzymatic steps in lipid biosynthesis are defined at the moleculargenetic level in several model organisms (Nohturfft and Zhang, 2009;Chapman and Ohlrogge, 2012;Henry et al, 2012), the signals and mechanisms regulating intracellular lipid homeostasis are less well defined (Nohturfft and Zhang, 2009;Hermansson et al, 2011, Holthuis andMenon, 2014), particularly in plants (Bonaventure et al, 2004;Kunz et al, 2009;Zhang et al, 2009;Fan et al, 2013a;Park 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). Disruption of the Arabidopsis CGI58-LIKE (CGI58L; Kelly et al, 2011) results in increased TAG accumulation, decreased jasmonate production, and altered responses to auxin, implying a role for CGI58L in lipid turnover and signaling (James et al, 2010;Park et al, 2013).…”

NMT1 and NMT3 N-Methyltransferase Activity Is Critical to Lipid Homeostasis, Morphogenesis, and Reproduction

“…TRIGLYCERIDE LIPASE (ATGLL) (Eastmond et al, 2006;Kelly et al 2011Kelly et al , 2013, and 514 also CGI58, which encodes an enzyme reported to have lipase, phospholipase and 515 lysophosphatidic acid acyltransferase activities (Ghosh et al, 2009) and has been suggested 516 to be involved in lipid turnover and signalling (James et al, 2010;Park et al, 2013), as well 517 as PEROXISOME ABC TRANSPORTER 1 (PXA1) whose encoded protein acts in fatty acid 518 transport in peroxisomes (De Marcos Lousa et al, 2013). No differential gene expression was 519 found except for a small increase and decrease in ATGLL and CGI58L expression, 520 respectively, in roots (Supplemental Fig.…”

The life of the peroxisome: from birth to death

“…Diverse substrates for -oxidation are imported via the PEROXISOME ABC TRANSPORTER 1/COMATOSE (PXA1/CTS) which can accept CoA esters and may cleave them upon transport [3] followed by reactivation by a peroxisomal acyl-CoA synthetase with the appropriate substrate specificity (Figure 1). The CTS/PXA1 interacting protein COMPARATIVE GENE IDENTIFICATION -58 (CGI-58) may regulate CTS/PXA1 activity in non-lipid storing tissues [4]. Peroxisomal -oxidation participates in the synthesis of benzoic acid, which acts as a precursor to various secondary metabolites, (see [5]) and 4-hydroxybenzoic acid, an intermediate in one of two independent pathways for the ubiquinone synthesis [6] ( Figure 1) .…”