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Ergosterol Turnover in Yeast: An Interplay between Biosynthesis and Transport

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Abstract

Sterols are important components of biological membranes that determine the physicochemical properties of lipid bilayer and regulate the functioning of membrane proteins. Being insoluble in water, sterols cannot diffuse between the membrane compartments separated by an aqueous phase. For this reason, distribution of sterols across cellular membranes is rather uneven. Membrane-to-membrane transport of sterols occurs mainly in a non-vesicular fashion and is provided by Lam and Osh proteins. In this review, we discuss the consequences of impairments in sterol biosynthesis and transport mostly relying on the studies performed on the model organism Saccharomyces cerevisiae. Despite the fact that molecular mechanisms underlying the functioning of Lam and Osh proteins are well established, the biological roles of these proteins are still unclear, because deletions of corresponding genes do not affect yeast phenotype. At the same time, disruptions in the biosynthesis of ergosterol, the major sterol of S. cerevisiae, lead to either cell death or reduced stress resistance. However, under certain conditions (e.g., mild salt or thermal stresses), a decrease in the ergosterol levels causes an increase in cell resistance. This suggests that the cells possess a mechanism facilitating rapid adjustment of the plasma membrane sterol content. We argue that the biological role of Lam proteins is, in particular, fast optimization of sterol composition of cell membranes.

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Abbreviations

ER:

endoplasmic reticulum

Lam proteins:

lipid transfer proteins anchored at the membrane contact sites

MCS:

membrane contact site

MDR:

multidrug resistance

ORD:

OSBP-related domain (400-a.a.-long lipid-bindingdomain)

OSBP:

oxysterolbinding protein

Osh proteins:

oxysterolbinding protein homologs

PI4P:

phosphatidylinositol 4 phosphate

PM:

plasma membrane

StART:

steroidogenic acute regulatory transfer

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Authors and Affiliations

  1. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991, Moscow, Russia

    S. S. Sokolov, F. F. Severin & D. A. Knorre

  2. Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119991, Moscow, Russia

    N. I. Trushina

  3. Sechenov First Moscow State Medical University, 119991, Moscow, Russia

    D. A. Knorre

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  1. S. S. Sokolov
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  2. N. I. Trushina
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  3. F. F. Severin
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Correspondence to S. S. Sokolov.

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Published in Russian in Biokhimiya, 2019, Vol. 84, No. 4, pp. 481–493.

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Sokolov, S.S., Trushina, N.I., Severin, F.F. et al. Ergosterol Turnover in Yeast: An Interplay between Biosynthesis and Transport. Biochemistry Moscow 84, 346–357 (2019). https://doi.org/10.1134/S0006297919040023

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  • DOI: https://doi.org/10.1134/S0006297919040023

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