Correlation of Lipid Accumulation in Yeasts with Possession of ATP: Citrate Lyase

Boulton, Chris A.; Ratledge, Colin

doi:10.1099/00221287-127-1-169

Cited by 90 publications

(88 citation statements)

References 17 publications

(11 reference statements)

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“…The extreme sensitivity of the process of citrate transport to inhibition by fatty-acyl-CoA esters is almost identical to that previously noted for the inhibition of ATP: citrate lyase in the oleaginous yeast Lipomyces starkeyi [19]. It is possible therefore that we are seeing a co-ordinated feedback inhibition on both citrate transport and the citrate lyase perhaps brought about by the association of the latter enzyme with the former activity.…”

Section: Discussionsupporting

confidence: 53%

“…Such an association has already been demonstrated with ATP: citrate lyase from rat liver with the outer mitochondrial membrane [50]. This inhibition pattern would then provide a stringent regulatory mechanism for either controlling the amount of lipid accumulated by an oleaginous yeast [19] or for ensuring that lipid biosynthesis was readily inhibited if degradation of the stored triacylglycerol was initiated for any reason. Either event could be envisaged as leading to the formation of small but critical concentrations of long-chain fatty-acyl-CoAs.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Regulation of Citrate Efflux from Mitochondria of Oleaginous and Non‐Oleaginous Yeass by Long‐Chain Fatty Acyl‐CoA Esters

Evans

Scragg

Ratledge

1983

European Journal of Biochemistry

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1. Citrate efflux from a wide range of yeast mitochondria was inhibited by long-chain fatty-acyl-CoA esters. 2. Fatty-acyl-CoA esters with chain lengths of between 14 and 18 carbons were the most potent inhibitors of 3. 50 % inhibition of citrate transport was observed using palmitoyl-CoA and oleoyl-CoA at approx. 4-5 pM 4. The inhibition with palmitoyl-CoA and oleoyl-CoA was competitive with L-malate. 5. The possibility that the fatty-acyl-CoA esters were exerting their effect by acting as detergent was eliminated because of the low concentrations used and appropriate comparisons being made with non-specific detergents. Although detergents inhibited citrate efflux they also released citrate by causing membrane damage.6. The effect of fatty-acyl-CoA esters on citrate efflux could be decreased by using higher mitochondrial protein levels and by adding bovine serum albumin.7. The possibility is discussed that this inhibition represents a genuine feedback inhibition which could regulate the amount of lipid being synthesized by an oleaginous yeast.citrate efflux which was unaffected by the fatty acids themselves.when the tricarboxylate carrier was saturated with L-malate as counter-anion.Lipid biosynthesis in oleaginous yeasts [I, 21 is dependent upon the presence of a cytosolic ATP: citrate lyase together with a means of producing the citrate in the mitochondria followed by efficient transport of it into the cytosol [3 -51. Efflux of citrate could be controlled by (a) limiting the amount of intramitochondrial citrate made available for binding to the citrate translocase in the inner mitochondrial membrane, (b) by the availability of cytosolic L-malate as counter-anion for the operation of the citrate-malate exchange and (c) by directly affecting the efficiency of the citrate carrier from promoting exchange. The importance of points (a) and (b) with regard to oleaginicity in yeasts has been discussed previously [5,6]. The direct regulation of the mitochondrial carrier by long-chain fatty-acyl-CoA esters forms the subject of this report.The inhibition of fatty acid biosynthesis by fatty-acyl-CoA esters has been well documented in both mammalian systems [7 -151 and in yeasts [7,16 -221. Much of this work has been related to the effect of these acyl-CoA esters upon the various enzymes involved in lipid biosynthesis and their possible regulatory roles [7]. In mammalian systems, workers have also studied the effect of long-chain fatty-acyl-CoA esters on the mitochondrial transport systems since these provide an obvious target for metabolic control in the cell [23 -281. Due to the importance of citrate, as a precursor to cytosolic acetylCoA, attention has been focussed on the inhibition of the tricarboxylate carrier by fatty-acyl-CoAs as a potential control point in fatty acid biosynthesis [29 -341. However, because of the potent surface-active properties of long-chain fatty-acylCoA esters there has been much speculation over their physiological significance in metabolic regulation [7 -10, 351. To date there have been n...

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Section: Discussionsupporting

confidence: 53%

Section: Discussionmentioning

confidence: 99%

Regulation of Citrate Efflux from Mitochondria of Oleaginous and Non‐Oleaginous Yeass by Long‐Chain Fatty Acyl‐CoA Esters

Evans

Scragg

Ratledge

1983

European Journal of Biochemistry

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“…Strains were propagated on BMM fructification medium (14), and spore germination was achieved on BMM with 0.5% sodium acetate. For transformation and DNA isolation, S. macrospora was cultivated in CM medium [1% glucose, 0.2% tryptone, 0.2% yeast extract, 0.15% KH 2 PO 4 , 0.05% KCl, 0.05% MgSO 4 , 0.37% NH 4 Cl, and 10 mg each of ZnSO 4 , Fe(II)Cl 2 , and MnCl 2 per liter].…”

Section: Methodsmentioning

confidence: 99%

Cell Differentiation during Sexual Development of the Fungus Sordaria macrospora Requires ATP Citrate Lyase Activity

Nowrousian

Masloff

Pöggeler

et al. 1999

Molecular and Cellular Biology

131

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During sexual development, mycelial cells from most filamentous fungi differentiate into typical fruiting bodies. Here, we describe the isolation and characterization of the Sordaria macrospora developmental mutant per5, which exhibits a sterile phenotype with defects in fruiting body maturation. Cytological investigations revealed that the mutant strain forms only ascus precursors without any mature spores. Using an indexed cosmid library, we were able to complement the mutant to fertility by DNA-mediated transformation. A single cosmid clone, carrying a 3.5-kb region able to complement the mutant phenotype, has been identified. Sequencing of the 3.5-kb region revealed an open reading frame of 2.1 kb interrupted by a 66-bp intron. The predicted polypeptide (674 amino acids) shows significant homology to eukaryotic ATP citrate lyases (ACLs), with 62 to 65% amino acid identity, and the gene was named acl1. The molecular mass of the S. macrospora ACL1 polypeptide is 73 kDa, as was verified by Western blot analysis with a hemagglutinin (HA) epitope-tagged ACL1 polypeptide. Immunological in situ detection of the HA-tagged polypeptide demonstrated that ACL is located within the cytosol. Sequencing of the mutant acl1 gene revealed a 1-nucleotide transition within the coding region, resulting in an amino acid substitution within the predicted polypeptide. Further evidence that ACL1 is essential for fruiting body maturation comes from experiments in which truncated and mutated versions of the acl1 gene were used for transformation. None of these copies was able to reconstitute the fertile phenotype in transformed per5 recipient strains. ACLs are usually involved in the formation of cytosolic acetyl coenzyme A (acetyl-CoA), which is used for the biosynthesis of fatty acids and sterols. Protein extracts from the mutant strain showed a drastic reduction in enzymatic activity compared to values obtained from the wild-type strain. Investigation of the time course of ACL expression suggests that ACL is specifically induced at the beginning of the sexual cycle and produces acetyl-CoA, which most probably is a prerequisite for fruiting body formation during later stages of sexual development. We discuss the contribution of ACL activity to the life cycle of S. macrospora.The fruiting body maturation of filamentous ascomycetes is an attractive model system to study multicellular development in eukaryotes. It involves the formation of the outer structures of the fruiting body but also development of mature ascospores within the fruiting body itself (for reviews, see references 31 and 47). Ascus development starts with the formation of female gametangia called ascogonia. The ascogenous cells are enveloped by sterile hyphae to form fruiting body precursors. Subsequent tissue differentiation gives rise to an outer pigmented peridial tissue, and following caryogamy, inner ascus initials embedded in sterile paraphyses are formed. Mature fruiting bodies from most ascomycetes harbor 200 to 400 asci, which after meiosis and postmeiotic di...

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“…Although it has long been established that the build-up of lipid storage reserves, mainly in the form of triacylglycerols, requires the presence of ACL to generate acetyl-CoA in the cytosol (Botham & Ratledge, 1979), the activity of this enzyme does not correlate with the amount of lipid that a particular micro-organism may accumulate (Boulton & Ratledge, 1981;Ratledge & Gilbert, 1985;Wynn et al, 1998). Indeed, a feature of lipid storage in microorganisms, and also in plants, is that the maximum amount of lipid that can be stored in an individual species appears to be under genetic control in that there seems to be an absolute ceiling beyond which further increases in lipid content cannot proceed.…”

Section: Characterization Of the Transformed Strainsmentioning

confidence: 99%

Malic enzyme: the controlling activity for lipid production? Overexpression of malic enzyme in Mucor circinelloides leads to a 2.5-fold increase in lipid accumulation

2007

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Correlation of Lipid Accumulation in Yeasts with Possession of ATP: Citrate Lyase

Cited by 90 publications

References 17 publications

Regulation of Citrate Efflux from Mitochondria of Oleaginous and Non‐Oleaginous Yeass by Long‐Chain Fatty Acyl‐CoA Esters

Regulation of Citrate Efflux from Mitochondria of Oleaginous and Non‐Oleaginous Yeass by Long‐Chain Fatty Acyl‐CoA Esters

Cell Differentiation during Sexual Development of the Fungus Sordaria macrospora Requires ATP Citrate Lyase Activity

Malic enzyme: the controlling activity for lipid production? Overexpression of malic enzyme in Mucor circinelloides leads to a 2.5-fold increase in lipid accumulation

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