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

Ida Elle , Karina Trankjær Simonsen , Louise Cathrine Braun Olsen , Pernille Kirstine Birck , Sidse Ehmsen , Simon Tuck , Thuc Timothy Le , Nils J. Faergeman (1)

1 Biochemistry and Molecular Biology

Acyl-CoA binding protein (ACBP) 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 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 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.

Mots clés: Life Sciences

Ida Elle, Karina Trankjær Simonsen, Louise Cathrine Braun Olsen, Pernille Kirstine Birck, Sidse Ehmsen, et al.. Tissue- and paralogue-specific functions of acyl-CoA-binding proteins in lipid metabolism in C. elegans. Biochemical Journal, 2011, 437 (2), pp.231-241. ⟨10.1042/BJ20102099⟩. ⟨hal-00605255⟩