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Rui, Y.N., Xu, Z., Patel, B., Chen, Z., Chen, D., Tito, A., David, G., Sun, Y., Stimming, E.F., Bellen, H.J., Cuervo, A.M., Zhang, S. (2015). Huntingtin functions as a scaffold for selective macroautophagy.  Nat. Cell Biol. 17(3): 262--275.
FlyBase ID
FBrf0227668
Publication Type
Research paper
Abstract

Selective macroautophagy is an important protective mechanism against diverse cellular stresses. In contrast to the well-characterized starvation-induced autophagy, the regulation of selective autophagy is largely unknown. Here, we demonstrate that Huntingtin, the Huntington disease gene product, functions as a scaffold protein for selective macroautophagy but it is dispensable for non-selective macroautophagy. In Drosophila, Huntingtin genetically interacts with autophagy pathway components. In mammalian cells, Huntingtin physically interacts with the autophagy cargo receptor p62 to facilitate its association with the integral autophagosome component LC3 and with Lys-63-linked ubiquitin-modified substrates. Maximal activation of selective autophagy during stress is attained by the ability of Huntingtin to bind ULK1, a kinase that initiates autophagy, which releases ULK1 from negative regulation by mTOR. Our data uncover an important physiological function of Huntingtin and provide a missing link in the activation of selective macroautophagy in metazoans.

PubMed ID
PubMed Central ID
PMC4344873 (PMC) (EuropePMC)
Related Publication(s)
Note

Huntingtin facilitates selective autophagy.
Gelman et al., 2015, Nat. Cell Biol. 17(3): 214--215 [FBrf0228256]

HTT/Huntingtin in selective autophagy and Huntington disease: A foe or a friend within?
Rui et al., 2015, Autophagy 11(5): 858--860 [FBrf0231044]

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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Nat. Cell Biol.
    Title
    Nature Cell Biology
    Publication Year
    1999-
    ISBN/ISSN
    1465-7392 1476-4679
    Data From Reference