Huntingtin functions as a scaffold for selective macroautophagy

Yan Ning Rui, Zhen Xu, Bindi Patel, Zhihua Chen, Dongsheng Chen, Antonio Tito, Gabriela David, Yamin Sun, Erin F. Stimming, Hugo J. Bellen, Ana Maria Cuervo, Sheng Zhang

Research output: Contribution to journalArticle

149 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)262-275
Number of pages14
JournalNature Cell Biology
Volume17
Issue number3
DOIs
StatePublished - Mar 2 2015

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Autophagy
Aptitude
Huntington Disease
Ubiquitin
Starvation
Drosophila
Phosphotransferases

ASJC Scopus subject areas

  • Cell Biology

Cite this

Rui, Y. N., Xu, Z., Patel, B., Chen, Z., Chen, D., Tito, A., ... Zhang, S. (2015). Huntingtin functions as a scaffold for selective macroautophagy. Nature Cell Biology, 17(3), 262-275. https://doi.org/10.1038/ncb3101

Huntingtin functions as a scaffold for selective macroautophagy. / Rui, Yan Ning; Xu, Zhen; Patel, Bindi; Chen, Zhihua; Chen, Dongsheng; Tito, Antonio; David, Gabriela; Sun, Yamin; Stimming, Erin F.; Bellen, Hugo J.; Cuervo, Ana Maria; Zhang, Sheng.

In: Nature Cell Biology, Vol. 17, No. 3, 02.03.2015, p. 262-275.

Research output: Contribution to journalArticle

Rui, YN, Xu, Z, Patel, B, Chen, Z, Chen, D, Tito, A, David, G, Sun, Y, Stimming, EF, Bellen, HJ, Cuervo, AM & Zhang, S 2015, 'Huntingtin functions as a scaffold for selective macroautophagy', Nature Cell Biology, vol. 17, no. 3, pp. 262-275. https://doi.org/10.1038/ncb3101
Rui YN, Xu Z, Patel B, Chen Z, Chen D, Tito A et al. Huntingtin functions as a scaffold for selective macroautophagy. Nature Cell Biology. 2015 Mar 2;17(3):262-275. https://doi.org/10.1038/ncb3101
Rui, Yan Ning ; Xu, Zhen ; Patel, Bindi ; Chen, Zhihua ; Chen, Dongsheng ; Tito, Antonio ; David, Gabriela ; Sun, Yamin ; Stimming, Erin F. ; Bellen, Hugo J. ; Cuervo, Ana Maria ; Zhang, Sheng. / Huntingtin functions as a scaffold for selective macroautophagy. In: Nature Cell Biology. 2015 ; Vol. 17, No. 3. pp. 262-275.
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