Oleate β-oxidation in yeast involves thioesterase but not Yor180c protein that is not a dienoyl-CoA isomerase

Ntamack, André G.; Karpichev, Igor V.; Gould, Stephen J.; Small, Gillian M.; Schulz, Horst

doi:10.1016/j.bbalip.2009.01.026

Cited by 9 publications

(8 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In higher eukaryotes, there are two mechanisms by which fatty acids can exit the peroxisome: a carnitine‐dependent route and a thioesterase‐dependent route . In yeast, evidence of involvement of PTE1, the peroxisomal acyl‐CoA thioesterase, in transferring acyl moieties out of peroxisomes was recently reported . Hence, the DHA β‐oxidation intermediates could be transported out of peroxisomes through either carnitine acetyltransferase (Cat2p), or the thioesterase (PTE1) dependent route, or both.…”

Section: Discussionmentioning

confidence: 99%

Expression of a type 2 diacylglycerol acyltransferase from Thalassiosira pseudonana in yeast leads to incorporation of docosahexaenoic acid β‐oxidation intermediates into triacylglycerol

Kazachkov

Jia

et al. 2013

The FEBS Journal

View full text Add to dashboard Cite

Glycerolipids of the marine diatom Thalassiosira pseudonana are enriched particularly with eicosapentaenoic acid (EPA), and also with an appreciable level of docosahexaenoic acid (DHA). The present study describes the functional characterization of a type 2 diacylglycerol acyltransferase (DGAT2, http://www.chem.qmul.ac.uk/iubmb/enzyme/EC2/3/1/20.html) from T. pseudonana, designated TpDGAT2, which catalyzes the final step of triacylglycerol (TAG) synthesis. Heterologous expression of this gene restored TAG formation in a yeast mutant devoid of TAG biosynthesis. TpDGAT2 was also shown to exert a large impact on the fatty acid profile of TAG. Its expression caused a 10–12% increase of 18:1 and a concomitant decrease of 16:0 relative to that of AtDGAT1(Arabidopsis thaliana). Furthermore, in the presence of the very‐long‐chain polyunsaturated fatty acids (VLCPUFA) EPA and DHA, TAG formed by TpDGAT2 displayed three‐ to six‐fold increases in the percentage of VLCPUFA relative to that of AtDGAT1 even though TpDGAT2 conferred much lower TAG‐synthetic activities than Arabidopsis DGAT1. Strikingly, when fed DHA, the yeast mutant expressing TpDGAT2 incorporated high levels of EPA and DHA isomers derived from DHA β‐oxidation. In contrast, no such phenomenon occurred in the cells expressing AtDGAT1. These results suggested that, in addition to the role in breaking down storage lipids, yeast peroxisomes also contribute to lipid synthesis by recycling acyl‐CoAs when a fatty acyl assembly system is available to capture and utilize the fatty acyl pools generated via β‐oxidation. Our study hence illustrated a case where the efficiency and substrate preference of an acyltransferase can elicit far reaching metabolic adjustments that affect TAG composition.

show abstract

Section: Discussionmentioning

confidence: 99%

Expression of a type 2 diacylglycerol acyltransferase from Thalassiosira pseudonana in yeast leads to incorporation of docosahexaenoic acid β‐oxidation intermediates into triacylglycerol

Kazachkov

Jia

et al. 2013

The FEBS Journal

View full text Add to dashboard Cite

show abstract

“…Gurvitz et al (1999) proposed that 3,5- cis -tetradecadienoyl-CoA is oxidized by the reductase-dependent pathway and involves the dienoyl isomerase Dci1. However, recent data also indicate that the thioesterase-dependent pathway, which involves the acyl-CoA thioesterase Tes1, is operative in S. cerevisiae (Ntamack et al 2009). …”

Section: Peroxisomesmentioning

confidence: 99%

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

2013

View full text Add to dashboard Cite

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.

show abstract

“…It has been suggested that acetate, generated from peroxisomal acetyl-CoA by thioesterases, might be able to exit the peroxisome (24,58). A number of predicted thioesterases occur in C. albicans and in A. nidulans while in S. cerevisiae a single peroxisomal enzyme (Tes1) is regulated by fatty acid induction, and deletion of TES1 results in slightly reduced growth on oleate (41). Alternatively, acetyl-CoA hydrolase could generate acetate (58).…”

Section: Vol 10 2011 Acetyl-carnitine Shuttle In Aspergillus Nidulamentioning

confidence: 99%

Role of Carnitine Acetyltransferases in Acetyl Coenzyme A Metabolism in Aspergillus nidulans

et al. 2011

View full text Add to dashboard Cite

The flow of carbon metabolites between cellular compartments is an essential feature of fungal metabolism. During growth on ethanol, acetate, or fatty acids, acetyl units must enter the mitochondrion for metabolism via the tricarboxylic acid cycle, and acetyl coenzyme A (acetyl-CoA) in the cytoplasm is essential for the biosynthetic reactions and for protein acetylation. Acetyl-CoA is produced in the cytoplasm by acetyl-CoA synthetase during growth on acetate and ethanol while ␤-oxidation of fatty acids generates acetyl-CoA in peroxisomes. The acetyl-carnitine shuttle in which acetyl-CoA is reversibly converted to acetyl-carnitine by carnitine acetyltransferase (CAT) enzymes is important for intracellular transport of acetyl units. In the filamentous ascomycete Aspergillus nidulans, a cytoplasmic CAT, encoded by facC, is essential for growth on sources of cytoplasmic acetyl-CoA while a second CAT, encoded by the acuJ gene, is essential for growth on fatty acids as well as acetate. We have shown that AcuJ contains an N-terminal mitochondrial targeting sequence and a C-terminal peroxisomal targeting sequence (PTS) and is localized to both peroxisomes and mitochondria, independent of the carbon source. Mislocalization of AcuJ to the cytoplasm does not result in loss of growth on acetate but prevents growth on fatty acids. Therefore, while mitochondrial AcuJ is essential for the transfer of acetyl units to mitochondria, peroxisomal localization is required only for transfer from peroxisomes to mitochondria. Peroxisomal AcuJ was not required for the import of acetyl-CoA into peroxisomes for conversion to malate by malate synthase (MLS), and export of acetyl-CoA from peroxisomes to the cytoplasm was found to be independent of FacC when MLS was mislocalized to the cytoplasm.The importance of understanding fungal carbon metabolism and its regulation has become increasingly apparent. This stems from studies of changes in metabolism accompanying fungal infections, development, and stress responses as well as the requirement for substrates for secondary metabolism (7,9,34,35,53). Furthermore, genome-wide studies of gene expression under different circumstances reveal the level of our ignorance of metabolic complexity. While carbon metabolism in the budding yeast, Saccharomyces cerevisiae, is best understood, it is widely recognized that this fungus is highly specialized in its preference for the fermentation of sugars to ethanol and the use of paralogous genes, derived from a whole-genome duplication in its evolutionary history, to encode different forms of enzymes for particular enzymatic reactions (20). The metabolism of another hemiascomycete, Candida albicans, has received attention recently because of its importance as a human pathogen, and there are many shared features with S. cerevisiae. Of special interest, however, is the extent to which the regulation of the expression of genes has been rewired such that the S. cerevisiae transcription factors used for controlling fundamental metabolic pathways may be different ...

show abstract

Oleate β-oxidation in yeast involves thioesterase but not Yor180c protein that is not a dienoyl-CoA isomerase

Cited by 9 publications

References 21 publications

Expression of a type 2 diacylglycerol acyltransferase from Thalassiosira pseudonana in yeast leads to incorporation of docosahexaenoic acid β‐oxidation intermediates into triacylglycerol

Expression of a type 2 diacylglycerol acyltransferase from Thalassiosira pseudonana in yeast leads to incorporation of docosahexaenoic acid β‐oxidation intermediates into triacylglycerol

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

Role of Carnitine Acetyltransferases in Acetyl Coenzyme A Metabolism in Aspergillus nidulans

Contact Info

Product

Resources

About