Fig. 9: Alterations in lipid metabolism induced by the lack of ACBD5. | Communications Biology

Fig. 9: Alterations in lipid metabolism induced by the lack of ACBD5.

From: Cerebellar and hepatic alterations in ACBD5-deficient mice are associated with unexpected, distinct alterations in cellular lipid homeostasis

Fig. 9: Alterations in lipid metabolism induced by the lack of ACBD5.

Fatty acid elongation is performed at the ER from stored LCFA. Peroxisomes might control FA over-elongation by a competitive import of VLCFA, requiring peroxisome-ER contact sites for their full productivity. ACBD5 disruption prevents peroxisomal import of VLCFA thereby accumulating substrates for elongation of VLCFA to UCLFA, which are subsequently incorporated into membrane lipids. Likewise the C24:6 n-3 precursor of DHA, which has to be chain-shortened by one round of peroxisomal β-oxidation is further elongated and desaturated to polyenoic PUFAs. Ether lipids are synthesized in peroxisomes up to the 1-O-alkyl-2-hydroxy-sn-glycerophosphate intermediates. Subsequent conversion to 1-O-alkyl-2-acyl-sn-glycerols and at last ligation of a PE or PC head group in sn3-position to yield the mature ether-phosphoglycerolipid is performed at the ER membrane. As revealed by lipidomics, ACBD5 disruption apparently induces formation of monoalkyl-diacyl-glycerols, which are ultimately rerouted to lipid droplets. Currently, the significance of peroxisome-ER contact sites is not fully understood but may contribute to a regulatory network controlling membrane ether-lipid formation.

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