Acyl-CoA-binding protein, Acb1p, is required for normal vacuole function and ceramide synthesis in Saccharomyces cerevisiae

Færgeman, Nils J.; Feddersen, Søren; Christiansen, Janne K.; Kobæk-Larsen, Morten; Schneiter, Roger; Ungermann, Christian; Mutenda, Kudzai E.; Roepstorff, Peter; Knudsen, Jens

doi:10.1042/bj20031949

Cited by 72 publications

(79 citation statements)

References 52 publications

(70 reference statements)

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“…A human ortholog encodes a 2-hydroxylase that can work on free fatty acids, probably of various chain lengths, whereas the yeast enzyme appears to work on fatty acids only once they are attached to ceramide [36]. The essential fatty acyl CoA binding protein, Acb1p, is also required for efficient ceramide synthesis in yeast [37], and the mammalian Acb1p homolog is essential for the viability of mammalian tissue-culture cells [38]. Acb1p is most likely essential for efficient delivery or presentation of very long-chain fatty acids to the ceramide synthase in yeast.…”

Section: Dihydroceramide Synthase (Dhcers) (Reaction Vi)mentioning

confidence: 99%

The ins and outs of sphingolipid synthesis

Futerman

Riezman

2005

Trends in Cell Biology

301

266

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Section: Dihydroceramide Synthase (Dhcers) (Reaction Vi)mentioning

confidence: 99%

The ins and outs of sphingolipid synthesis

Futerman

Riezman

2005

Trends in Cell Biology

301

266

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“…This phenotype is actually quite reminiscent of the depletion of the acyl CoA binding protein (Acb1), which does not seem to be directly connected to the fusion reaction. 166 Generally, it appears that vacuole dynamics are linked to the metabolic state of the cell and potentially connected to autophagy. 17 How sensing of nutrients occurs at the vacuole is not yet known.…”

Section: The Vacuole Fusion Machinerymentioning

confidence: 99%

Yeast vacuole fusion: A model system for eukaryotic endomembrane dynamics

Ostrowicz¹,

Meiringer²,

Ungermann³

2008

Autophagy

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101

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Vesicular transport in eukaryotic cells is concluded with the consumption of the vesicle at the target membrane. This fusion process relies on Rabs, tethers and SNAREs. Powerful in vitro fusion systems using isolated organelles were crucial to obtain insights into the underlying mechanism of membrane fusionfrom the initiation of fusion to lipid bilayer mixing. Among these systems, yeast vacuoles turned out to be particularly useful as they can be manipulated biochemically and genetically. Studies relying on this organelle have revealed insights into the connection of vacuole fusion to endomembrane biogenesis. A number of fusion factors were identified and characterized over the last several years, and placed into the fusion cascade. Within this review, we will present and discuss the current state of our knowledge on vacuole fusion.

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“…Targeted disruption of the yeast ACBP gene (ACB1) revealed that ACBP deficiency results in increased levels of C18:0 acyl-CoA esters and a decrease in the amount of total C26:0 fatty acids, indicating that transport of FA toward elongation is impaired by lack of ACBP. Furthermore, sphingolipid and ceramide amounts were reduced, membrane structure was altered, and vesicular transport was compromised (23)(24)(25).…”

mentioning

confidence: 99%

Disruption of the Acyl-CoA-binding Protein Gene Delays Hepatic Adaptation to Metabolic Changes at Weaning

Neess¹,

Bloksgaard²,

Bek³

et al. 2011

Journal of Biological Chemistry

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The mouse acyl-CoA-binding protein (ACBP) 5 /diazepam binding inhibitor is a 10-kDa intracellular protein consisting of 86 amino acids. It is highly conserved throughout evolution and expressed in all cell types in the eukaryotes investigated (1, 2). This, together with the characteristics of the ACBP promoter (3, 4), implies a housekeeping function of the gene. However, expression levels vary markedly between tissues (5) and in response to different metabolic stimuli (6 -9), thereby indicating that ACBP might perform more specialized functions in some cell types. The ACBP protein binds C 14 -C 22 acyl-CoA esters with high affinity and specificity (10, 11) and has very little or no affinity toward other ligands (11-13). From in vitro studies, ACBP is known to protect acyl-CoA esters from hydrolysis (14 -16) and to relieve acyl-CoA inhibition of a number of enzymes, including long chain acyl-CoA synthetase, acetyl-CoA carboxylase (ACC), adenine nucleotide translocase, fatty acid synthetase (FAS), carnitine palmitoyltransferase, and acyl-CoA:cholesterol acyltransferase (9, 16 -18). In addition, ACBP is known to donate acyl-CoA esters to phospholipid, glycerolipid, and cholesteryl ester (CE) synthesis (14, 18 -21). Finally, proteolytic products of secreted ACBP have been shown to have signaling functions in Dictyostelium as well as mammalian cells (22). Targeted disruption of the yeast ACBP gene (ACB1) revealed that ACBP deficiency results in increased levels of C18:0 acyl-CoA esters and a decrease in the amount of total C26:0 fatty acids, indicating that transport of FA toward elongation is impaired by lack of ACBP. Furthermore, sphingolipid and ceramide amounts were reduced, membrane structure was altered, and vesicular transport was compromised (23-25).The functions of ACBP in lipid metabolism have been further studied in different mammalian cell culture systems and animal models by both knockdown strategies and overexpression of the protein. It has been reported that knockdown of ACBP by small interfering RNA causes growth arrest and lethality in three different mammalian cell lines (26); however, data from our laboratory show that ACBP can be knocked down in many different cell systems without affecting growth and survival (27). 6 Recently, knockdown of ACBP in HepG2 cells was shown to suppress the expression of a number of genes involved in lipid biosynthesis and lead to decreased levels of saturated and monounsaturated fatty acids (28). In 3T3-L1 preadipocytes, knockdown of ACBP caused a mild impairment of adipocyte differentiation and accumulation of triacylglycerol (TAG) (27), whereas overexpression of ACBP in McA-RH7777 rat hepatoma cells resulted in increased intracellular TAG accumulation (29). Overexpression of ACBP in transgenic mice resulted in accumulation of different lipid classes, including TAG in the liver (30). These results suggest *

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Acyl-CoA-binding protein, Acb1p, is required for normal vacuole function and ceramide synthesis in Saccharomyces cerevisiae

Cited by 72 publications

References 52 publications

The ins and outs of sphingolipid synthesis

The ins and outs of sphingolipid synthesis

Yeast vacuole fusion: A model system for eukaryotic endomembrane dynamics

Disruption of the Acyl-CoA-binding Protein Gene Delays Hepatic Adaptation to Metabolic Changes at Weaning

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