The Sphinx and the egg: Evolutionary enigmas of the (glyco)sphingolipid biosynthetic pathway.

Autor: Biran A; Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 7610001, Israel., Santos TCB; Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 7610001, Israel., Dingjan T; Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 7610001, Israel. Electronic address: tamir.dingjan@weizmann.ac.il., Futerman AH; Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 7610001, Israel.
Jazyk: angličtina
Zdroj: Biochimica et biophysica acta. Molecular and cell biology of lipids [Biochim Biophys Acta Mol Cell Biol Lipids] 2024 Apr; Vol. 1869 (3), pp. 159462. Date of Electronic Publication: 2024 Feb 01.
DOI: 10.1016/j.bbalip.2024.159462
Abstrakt: In eukaryotes, the de novo synthesis of sphingolipids (SLs) consists of multiple sequential steps which are compartmentalized between the endoplasmic reticulum and the Golgi apparatus. Studies over many decades have identified the enzymes in the pathway, their localization, topology and an array of regulatory mechanisms. However, little is known about the evolutionary forces that underly the generation of this complex pathway or of its anteome, i.e., the metabolic pathways that converge on the SL biosynthetic pathway and are essential for its activity. After briefly describing the pathway, we discuss the mechanisms by which the enzymes of the SL biosynthetic pathway are targeted to their different subcellular locations, how the pathway per se may have evolved, including its compartmentalization, and the relationship of the pathway to eukaryogenesis. We discuss the circular interdependence of the evolution of the SL pathway, and comment on whether current Darwinian evolutionary models are able to provide genuine mechanistic insight into how the pathway came into being.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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