Comparative Gene Identification-58 (CGI-58) Promotes Autophagy as a Putative Lysophosphatidylglycerol Acyltransferase

Zhang, Jun; Xu, Dan; Nie, Jia; Han, Ruili; Zhai, Yonggong; Shi, Yuguang

doi:10.1074/jbc.m114.573857

Cited by 34 publications

(24 citation statements)

References 48 publications

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“…It is important to note that other proteins have been mistakenly identified as LPAAT enzymes due to similar problems with affinity co-purification of bacterial LPAATs [107]. Another recent report also suggested that CGI-58 instead possesses intrinsic lysophosphatidylglycerol acyltransferase (LPGAT) activity to convert lysophosphatidylglycerols (LPG) to phosphatidylglycerol (PG) [108]. However, CGI-58 knockdown in mouse liver is associated with marked accumulation of PG lipids, which is inconsistent with a LPGAT activity for CGI-58 [41].…”

Section: Conclusion and Perspectives: The Continued Search For Amentioning

confidence: 99%

“…This work showed that CGI-58 competes for a caspase binding site on beclin 1, thereby blunting caspase-mediated cleavage of beclin 1, and also showed that CGI-58 and beclin 1 expression levels were correlated in human colorectal cancer tissue [94]. Another recent study showed that CGI-58 regulates the autophagy of mitochondria, a process known as “mitophagy” [108]. This study showed CGI-58 overexpression stimulated the activity of 5’-AMP-activated protein kinase (AMPK) and diminished the signaling of the mammalian target of rapamycin complex 1 (mTORC1), both of which are major regulatory nodes in autophagy activation [108].…”

Section: Conclusion and Perspectives: The Continued Search For Amentioning

confidence: 99%

“…Another recent study showed that CGI-58 regulates the autophagy of mitochondria, a process known as “mitophagy” [108]. This study showed CGI-58 overexpression stimulated the activity of 5’-AMP-activated protein kinase (AMPK) and diminished the signaling of the mammalian target of rapamycin complex 1 (mTORC1), both of which are major regulatory nodes in autophagy activation [108]. Although additional work is needed, these studies provide support for the idea that CGI-58 may regulate cellular TAG storage via regulation of lipophagy and mitophagy.…”

Section: Conclusion and Perspectives: The Continued Search For Amentioning

confidence: 99%

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Critical roles for α/β hydrolase domain 5 (ABHD5)/comparative gene identification-58 (CGI-58) at the lipid droplet interface and beyond

Brown

2017

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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Mutations in the gene encoding comparative gene identification 58 (CGI-58), also known as α β hydrolase domain-containing 5 (ABHD5), cause neutral lipid storage disorder with ichthyosis (NLSDI). This inborn error in metabolism is characterized by ectopic accumulation of triacylglycerols (TAG) within cytoplasmic lipid droplets in multiple cell types. Studies over the past decade have clearly demonstrated that CGI-58 is a potent regulator of TAG hydrolysis in the disease-relevant cell types. However, despite the reproducible genetic link between CGI-58 mutations and TAG storage, the molecular mechanisms by which CGI-58 regulates TAG hydrolysis are still incompletely understood. It is clear that CGI-58 can regulate TAG hydrolysis by activating the major TAG hydrolase adipose triglyceride lipase (ATGL), yet CGI-58 can also regulate lipid metabolism via mechanisms that do not involve ATGL. This review highlights recent progress made in defining the physiologic and biochemical function of CGI-58, and its broader role in energy homeostasis.

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Section: Conclusion and Perspectives: The Continued Search For Amentioning

confidence: 99%

Section: Conclusion and Perspectives: The Continued Search For Amentioning

confidence: 99%

Section: Conclusion and Perspectives: The Continued Search For Amentioning

confidence: 99%

See 1 more Smart Citation

Critical roles for α/β hydrolase domain 5 (ABHD5)/comparative gene identification-58 (CGI-58) at the lipid droplet interface and beyond

Brown

2017

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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“…An intrinsic lysophosphatidylglycerol acyltransferase (LPGAT) activity had been reported for murine ABHD5/ CGI-58 (70). However, this is currently under debate, as PGs are actually increased in hepatocytes of ABHD5 knockdown mice (28), and a more recent publication could not confirm this activity for mouse and plant ABHD5 (61).…”

Section: Discussionmentioning

confidence: 99%

The α/β-hydrolase domain-containing 4- and 5-related phospholipase Pummelig controls energy storage in Drosophila

Hehlert

Hofferek

Heier

et al. 2019

Journal of Lipid Research

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Supplementary key words lipid and lipoprotein metabolism • obesity • storage diseases • phospholipids/metabolism • Malpighian tubules • adipose triglyceride lipase • Brummer (Drosophila melanogaster adipose triglyceride lipase)Organismal energy homeostasis is continuously challenged by fluctuating environmental and internal conditions, which require a fast and precisely controlled adaption to energy needs. To maintain this homeostasis, organisms as different as yeast, plants, nematodes, flies, mice, and humans accumulate energy stores during periods of food supply. Whenever energy expenditure exceeds energy intake, these energy stores become mobilized and catabolized to ensure permanent energy balance. Lipids, in particular triglycerides (TGs), are the calorically most important energy depots in eukaryotic organisms. Besides their pivotal function as metabolic fuel, i.e., as a source Abstract Triglycerides (TGs) are the main energy storage form that accommodates changing organismal energy demands. In Drosophila melanogaster, the TG lipase Brummer is centrally important for body fat mobilization. Its gene brummer (bmm) encodes the ortholog of mammalian adipose TG lipase, which becomes activated by /-hydrolase domaincontaining 5 (ABHD5/CGI-58), one member of the paralogous gene pair, /-hydrolase domain-containing 4 (ABHD4) and ABHD5. In Drosophila, the pummelig (puml) gene encodes the single sequence-related protein to mammalian ABHD4/ ABHD5 with unknown function. We generated puml deletion mutant flies, that were short-lived as a result of lipid metabolism changes, stored excess body fat at the expense of glycogen, and exhibited ectopic fat storage with altered TG FA profile in the fly kidneys, called Malpighian tubules. TG accumulation in puml mutants was not associated with increased food intake but with elevated lipogenesis; starvation-induced lipid mobilization remained functional. Despite its structural similarity to mammalian ABHD5, Puml did not stimulate TG lipase activity of Bmm in vitro. Rather, Puml acted as a phospholipase that localized on lipid droplets, mitochondria, and peroxisomes. Together, these results show that the ABHD4/5 family member Puml is a versatile phospholipase that regulates Drosophila body fat storage and energy metabolism.-Hehlert, P

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“…More recently, studies have demonstrated that human CGI-58 has lysophosphatidic acid (LPA) acyltransferase (Ghosh et al, 2008a) and lysophosphatidylglycerol (LPG) acyltransferase (Zhang et al, 2014) activities. In various cancers, high levels of ABHD11 mRNA transcripts have been reported, but the role of this enzyme in cancer metabolism is not known.…”

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confidence: 99%

The Arabidopsis ABHD11 Mutant Accumulates Polar Lipids in Leaves as a Consequence of Absent Acylhydrolase Activity

et al. 2015

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Alpha/beta hydrolase domain (ABHD)-containing proteins are structurally related with diverse catalytic activities. In various species, some ABHD proteins have been characterized and shown to play roles in lipid homeostasis. However, little is known about ABHD proteins in plants. Here, we characterized AT4G10030 (AtABHD11), an Arabidopsis (Arabidopsis thaliana) homolog of a human ABHD11 gene. In silico analyses of AtABHD11 revealed homology with other plant species with a conserved GXSXG lipid motif. Interestingly, Arabidopsis abhd11 mutant plants exhibited an enhanced growth rate compared with wildtype plants. Quantitative analyses of the total lipids showed that the mutant abhd11 has a high amount of phospholipid and galactolipid in Arabidopsis leaves. The overexpression of AtABHD11 in Escherichia coli led to a reduction in phospholipid levels. The bacterially expressed recombinant AtABHD11 hydrolyzed lyso(phospho)lipid and monoacylglycerol. Furthermore, using whole-genome microarray and real-time PCR analyses of abhd11 and wild-type plants, we noted the up-regulation of MGD1, -2, and -3 and DGD1. Together, these findings suggested that AtABHD11 is a lyso(phospho)lipase. The disruption of AtABHD11 caused the accumulation of the polar lipids in leaves, which in turn promoted a higher growth rate compared with wild-type plants.

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Comparative Gene Identification-58 (CGI-58) Promotes Autophagy as a Putative Lysophosphatidylglycerol Acyltransferase

Cited by 34 publications

References 48 publications

Critical roles for α/β hydrolase domain 5 (ABHD5)/comparative gene identification-58 (CGI-58) at the lipid droplet interface and beyond

Critical roles for α/β hydrolase domain 5 (ABHD5)/comparative gene identification-58 (CGI-58) at the lipid droplet interface and beyond

The α/β-hydrolase domain-containing 4- and 5-related phospholipase Pummelig controls energy storage in Drosophila

The Arabidopsis ABHD11 Mutant Accumulates Polar Lipids in Leaves as a Consequence of Absent Acylhydrolase Activity

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