Abstract

Sterols are essential for several physiological processes in most eukaryotes. Sterols regulate membrane homeostasis and participate in different signalling pathways not only as precursors of steroid hormones and vitamins, but also through its role in the formation of lipid rafts. Two major types of sterols, cholesterol and ergosterol, have been described so far in the opisthokonts, the clade that comprise animals, fungi and their unicellular relatives. Cholesterol predominates in derived bilaterians, whereas ergosterol is what generally defines fungi. We here characterize, by a combination of bioinformatic and biochemical analyses, the sterol metabolism in the filasterean Capsaspora owczarzaki, a close unicellular relative of animals that is becoming a model organism. We found that C. owczarzaki sterol metabolism combines enzymatic activities that are usually considered either characteristic of fungi or exclusive to metazoans. Moreover, we observe a differential transcriptional regulation of this metabolism across its life cycle. Thus, C. owczarzaki alternates between synthesizing 7-dehydrocholesterol de novo, which happens at the cystic stage, and the partial conversion—via a novel pathway—of incorporated cholesterol into ergosterol, the characteristic fungal sterol, in the filopodial and aggregative stages.

Highlights

  • Sterols are essential membrane components of most eukaryotic cells, having fundamental structural and signalling functions

  • Our data demonstrate that C. owczarzaki possesses a peculiar repertoire of sterol metabolism genes, including the complete canonical ergosterol pathway typical of fungi as well as other sterol-metabolism-related genes not involved in this pathway

  • This suggests that sterol metabolism in C. owczarzaki combines enzymatic activities that are usually considered either characteristic of fungi or exclusive to metazoans

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Summary

Introduction

Sterols are essential membrane components of most eukaryotic cells, having fundamental structural and signalling functions. Sterols participate in regulating membrane fluidity and permeability barrier properties [1]. Together with sphingolipids, sterols are involved in the formation of the lipid rafts, regions of reduced fluidity that selectively incorporate proteins involved in concerted functions such as cell-to-cell recognition, adhesion and communication [5,6]. Sterols play a role in many cellular processes crucial for the development and homeostasis of multicellular organisms, being critical to cell-to-cell communication processes [7,8,9,10,11]. Alterations in sterol composition and biosynthesis produce several diseases [12]

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