Tissue- and paralogue-specific functions of acyl-CoA-binding proteins in lipid metabolism in Caenorhabditis elegans

ACBP (acyl-CoA-binding protein) is a small primarily cytosolic protein that binds acyl-CoA esters with high specificity and affinity. ACBP has been identified in all eukaryotic species, indicating that it performs a basal cellular function. However, differential tissue expression and the existence of several ACBP paralogues in many eukaryotic species indicate that these proteins serve distinct functions. The nematode Caenorhabditis elegans expresses seven ACBPs: four basal forms and three ACBP domain proteins. We find that each of these paralogues is capable of complementing the growth of ACBP-deficient yeast cells, and that they exhibit distinct temporal and tissue expression patterns in C. elegans. We have obtained loss-of-function mutants for six of these forms. All single mutants display relatively subtle phenotypes; however, we find that functional loss of ACBP-1 leads to reduced triacylglycerol (triglyceride) levels and aberrant lipid droplet morphology and number in the intestine. We also show that worms lacking ACBP-2 show a severe decrease in the β-oxidation of unsaturated fatty acids. A quadruple mutant, lacking all basal ACBPs, is slightly developmentally delayed, displays abnormal intestinal lipid storage, and increased β-oxidation. Collectively, the present results suggest that each of the ACBP paralogues serves a distinct function in C. elegans.

Simonsen, Karina T (författare)
Olsen, Louise C B (författare)
Birck, Pernille K (författare)
Ehmsen, Sidse (författare)
Tuck, Simon,1961-Umeå universitet,Umeå centrum för molekylär medicin (UCMM),Simon Tuck(Swepub:umu)situ0001 (författare)
Le, Thuc T (författare)
Færgeman, Nils J (författare)
Umeå universitetUmeå centrum för molekylär medicin (UCMM) (creator_code:org_t)

Av författaren/redakt...: Elle, Ida C; Simonsen, Karina ...; Olsen, Louise C ...; Birck, Pernille ...; Ehmsen, Sidse; Tuck, Simon, 196 ...; visa fler...; Le, Thuc T; Færgeman, Nils J; visa färre...

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