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Regulated biogenesis and targeting of monotopic squalene monooxygenase requires the GET pathway

ABSTRACT: This study investigated get3 mutant yeast cell. Proteins of the GET pathway are involved in targeting of C-terminally anchored transmembrane proteins and protection against lipotoxicity. Get3 cells revealed an altered ergosterol production and susceptibility towards a sterol synthesis inhibiting drug terbinafine. Furthermore, we identified a member of a non-canonical GET pathway client, a monotopic membrane protein squalene monooxygenase Erg1 that may be responsible for the susceptibility of Get3 mutant to lipotoxic agents.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Saccharomyces Cerevisiae (baker's Yeast)

SUBMITTER: Ivan Silbern

LAB HEAD: Prof. Dr. Henning Urlaub

PROVIDER: PXD027705 | Pride | 2022-06-09

REPOSITORIES: Pride

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Regulated targeting of the monotopic hairpin membrane protein Erg1 requires the GET pathway.

Farkas Ákos Á Urlaub Henning H Bohnsack Katherine E KE Schwappach Blanche B

The Journal of cell biology 20220519 6

The guided entry of tail-anchored proteins (GET) pathway targets C-terminally anchored transmembrane proteins and protects cells from lipotoxicity. Here, we reveal perturbed ergosterol production in ∆get3 cells and demonstrate the sensitivity of GET pathway mutants to the sterol synthesis inhibiting drug terbinafine. Our data uncover a key enzyme of sterol synthesis, the hairpin membrane protein squalene monooxygenase (Erg1), as a non-canonical GET pathway client, thus rationalizing the lipotoxi ...[more]

PMID: 35587358

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