Mevalonate pathway regulates cell size homeostasis and proteostasis through autophagy

Teemu P. Miettinen (Lead / Corresponding author), Mikael Bjorklund (Lead / Corresponding author)

    Research output: Contribution to journalArticlepeer-review

    58 Citations (Scopus)
    159 Downloads (Pure)

    Abstract

    Balance between cell growth and proliferation determines cell size homeostasis, but little is known about how metabolic pathways are involved in the maintenance of this balance. Here, we perform a screen with a library of clinically used drug molecules for their effects on cell size. We find that statins, inhibitors of the mevalonate pathway, reduce cell proliferation and increase cell size and cellular protein density in various cell types, including primary human cells. Mevalonate pathway effects on cell size and protein density are mediated through geranylgeranylation of the small GTPase RAB11, which is required for basal autophagic flux. Our results identify the mevalonate pathway as a metabolic regulator of autophagy and expose a paradox in the regulation of cell size and proteostasis, where inhibition of an anabolic pathway can cause an increase in cell size and cellular protein density.

    Original languageEnglish
    Pages (from-to)2610-2620
    Number of pages11
    JournalCell Reports
    Volume13
    Issue number11
    Early online date10 Dec 2015
    DOIs
    Publication statusPublished - 22 Dec 2015

    ASJC Scopus subject areas

    • General Biochemistry,Genetics and Molecular Biology

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