The emerging role of acyl-CoA thioesterases and acyltransferases in regulating peroxisomal lipid metabolism

Hunt, Mary C.; Siponen, M.I.; Alexson, Stefan E.H.

doi:10.1016/j.bbadis.2012.03.009

Cited by 151 publications

(147 citation statements)

References 115 publications

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“…The complex role of these enzymes in lipid metabolism has been previously documented, particularly in animals (Hunt et al, 2012). Mammalian ACOT8, the closest homolog to the two Arabidopsis peroxisomal ACOTs (ACH1 and ACH2), showed high activities toward a broad range of acyl-CoA substrates and was strongly inhibited by CoA, suggesting that ACOT8 is involved in the regulation of the intracellular levels of acyl-CoAs, free fatty acids, and CoA (Hunt et al, 2002;Ofman et al, 2002).…”

Section: Ach2 An Ach Involved In the Hydrolysis Of Long-chain Fatty mentioning

confidence: 99%

Systematic Phenotypic Screen of Arabidopsis Peroxisomal Mutants Identifies Proteins Involved in β-Oxidation

Cassin-Ross

2014

Plant Physiology

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Peroxisomes are highly dynamic and multifunctional organelles essential to development. Plant peroxisomes accommodate a multitude of metabolic reactions, many of which are related to the b-oxidation of fatty acids or fatty acid-related metabolites. Recently, several dozens of novel peroxisomal proteins have been identified from Arabidopsis (Arabidopsis thaliana) through in silico and experimental proteomic analyses followed by in vivo protein targeting validations. To determine the functions of these proteins, we interrogated their transfer DNA insertion mutants with a series of physiological, cytological, and biochemical assays to reveal peroxisomal deficiencies. Sugar dependence and 2,4-dichlorophenoxybutyric acid and 12-oxo-phytodienoic acid response assays uncovered statistically significant phenotypes in b-oxidation-related processes in mutants for 20 of 27 genes tested. Additional investigations uncovered a subset of these mutants with abnormal seed germination, accumulation of oil bodies, and delayed degradation of long-chain fatty acids during early seedling development. Mutants for seven genes exhibited deficiencies in multiple assays, strongly suggesting the involvement of their gene products in peroxisomal b-oxidation and initial seedling growth. Proteins identified included isoforms of enzymes related to b-oxidation, such as acyl-CoA thioesterase2, acyl-activating enzyme isoform1, and acyl-activating enzyme isoform5, and proteins with functions previously unknown to be associated with b-oxidation, such as Indigoidine synthase A, Senescence-associated protein/B12D-related protein1, Betaine aldehyde dehydrogenase, and Unknown protein5. This multipronged phenotypic screen allowed us to reveal b-oxidation proteins that have not been discovered by single assay-based mutant screens and enabled the functional dissection of different isoforms of multigene families involved in b-oxidation.

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Section: Ach2 An Ach Involved In the Hydrolysis Of Long-chain Fatty mentioning

confidence: 99%

Systematic Phenotypic Screen of Arabidopsis Peroxisomal Mutants Identifies Proteins Involved in β-Oxidation

Cassin-Ross

2014

Plant Physiology

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“…Thus, the peroxisomal -oxidation of LCFAs produces chain-shortened acyl-CoAs (43) that can be hydrolyzed inside peroxisomes by distinct acyl-CoA thioesterases and released into the cytosol. In addition, peroxisomes are also equipped with carnitineacetyl and carnitine-octanoyl transferases, and thus shortened acyl-CoAs are converted into carnitine esters for the supply to mitochondria [reviewed in (44)]. …”

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confidence: 99%

Short- and medium-chain fatty acids in energy metabolism: the cellular perspective

Schönfeld

Wojtczak

2016

Journal of Lipid Research

753

523

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“…A third group of FAAH substrates, the amides of long-chain fatty acids with taurine [N-acyl-taurines (NATs)], has been identified in liver and other rodent tissues (9,10). The NATs may be produced through enzyme-dependent conjugation of fatty acyl-CoA with taurine-catalyzed by the peroxisomal acyltransferase, acyl-CoA amino acid N-acyltransferase-1 (11,12)-and have demonstrated biological activity in several cellular systems (13,14). Their roles in physiology remain unknown, however.…”

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confidence: 99%

Endogenous N -acyl taurines regulate skin wound healing

Sasso

Pontis

Armirotti

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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The intracellular serine amidase, fatty acid amide hydrolase (FAAH), degrades a heterogeneous family of lipid-derived bioactive molecules that include amides of long-chain fatty acids with taurine [N-acyl-taurines (NATs)]. The physiological functions of the NATs are unknown. Here we show that genetic or pharmacological disruption of FAAH activity accelerates skin wound healing in mice and stimulates motogenesis of human keratinocytes and differentiation of human fibroblasts in primary cultures. Using untargeted and targeted lipidomics strategies, we identify two longchain saturated NATs-N-tetracosanoyl-taurine [NAT(24:0)] and N-eicosanoyl-taurine [NAT(20:0)]-as primary substrates for FAAH in mouse skin, and show that the levels of these substances sharply decrease at the margins of a freshly inflicted wound to increase again as healing begins. Additionally, we demonstrate that local administration of synthetic NATs accelerates wound closure in mice and stimulates repair-associated responses in primary cultures of human keratinocytes and fibroblasts, through a mechanism that involves tyrosine phosphorylation of the epidermal growth factor receptor and an increase in intracellular calcium levels, under the permissive control of transient receptor potential vanilloid-1 receptors. The results point to FAAH-regulated NAT signaling as an unprecedented lipid-based mechanism of woundhealing control in mammalian skin, which might be targeted for chronic wound therapy.FAAH | N-acyl taurines | FAEs | fibroblasts | keratinocytes

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The emerging role of acyl-CoA thioesterases and acyltransferases in regulating peroxisomal lipid metabolism

Cited by 151 publications

References 115 publications

Systematic Phenotypic Screen of Arabidopsis Peroxisomal Mutants Identifies Proteins Involved in β-Oxidation

Systematic Phenotypic Screen of Arabidopsis Peroxisomal Mutants Identifies Proteins Involved in β-Oxidation

Short- and medium-chain fatty acids in energy metabolism: the cellular perspective

Endogenous N -acyl taurines regulate skin wound healing

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