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Resources » Paper

Hertel A et al. (2022) Cell Rep "USP32-regulated LAMTOR1 ubiquitination impacts mTORC1 activation and autophagy induction."

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  • Comments on Hertel A et al. (2022) Cell Rep "USP32-regulated LAMTOR1 ubiquitination impacts mTORC1 activation and autophagy induction." (0)

  • Overview

    PMID:
    36476874
    DOI:
    10.1016/j.celrep.2022.111653
    Status:
    Publication type:
    Journal_article
    WormBase ID:
    WBPaper00064822

    Hertel A, Alves LM, Dutz H, Tascher G, Bonn F, Kaulich M, Dikic I, Eimer S, Steinberg F, & Bremm A (2022). USP32-regulated LAMTOR1 ubiquitination impacts mTORC1 activation and autophagy induction. Cell Rep, 41, 111653. doi:10.1016/j.celrep.2022.111653

    The endosomal-lysosomal system is a series of organelles in the endocytic pathway that executes trafficking and degradation of proteins and lipids and mediates the internalization of nutrients and growth factors to ensure cell survival, growth, and differentiation. Here, we reveal regulatory, non-proteolytic ubiquitin signals in this complex system that are controlled by the enigmatic deubiquitinase USP32. Knockout (KO) of USP32 in primary hTERT-RPE1 cells results among others in hyperubiquitination of the Ragulator complex subunit LAMTOR1. Accumulation of LAMTOR1 ubiquitination impairs its interaction with the vacuolar H<sup>+</sup>-ATPase, reduces Ragulator function, and ultimately limits mTORC1 recruitment. Consistently, in USP32 KO cells, less mTOR kinase localizes to lysosomes, mTORC1 activity is decreased, and autophagy is induced. Furthermore, we demonstrate that depletion of USP32 homolog CYK-3 in Caenorhabditis elegans results in mTOR inhibition and autophagy induction. In summary, we identify a control mechanism of the mTORC1 activation cascade at lysosomes via USP32-regulated LAMTOR1 ubiquitination.

    Authors: Hertel A, Alves LM, Dutz H, Tascher G, Bonn F, Kaulich M, Dikic I, Eimer S, Steinberg F, Bremm A


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