Myristoylation confers noncanonical AMPK functions in autophagy selectivity and mitochondrial surveillance

Jiyong Liang, Zhi Xiang Xu, Zhiyong Ding, Yiling Lu, Qinghua Yu, Kaitlin D. Werle, Ge Zhou, Yun Yong Park, Guang Peng, Michael J. Gambello, Gordon B. Mills

    Research output: Contribution to journalArticle

    46 Scopus citations

    Abstract

    AMP-activated protein kinase (AMPK) plays a central role in cellular energy sensing and bioenergetics. However, the role of AMPK in surveillance of mitochondrial damage and induction of mitophagy remains unclear. We demonstrate herein that AMPK is required for efficient mitophagy. Mitochondrial damage induces a physical association of AMPK with ATG16-ATG5-12 and an AMPK-dependent recruitment of the VPS34 and ATG16 complexes with the mitochondria. Targeting AMPK to the mitochondria is both sufficient to induce mitophagy and to promote cell survival. Recruitment of AMPK to the mitochondria requires N-myristoylation of AMPKβ by the type-I N-myristoyltransferase 1 (NMT1). Our data support a spatiotemporal model wherein recruitment of AMPK in association with components of the VPS34 and ATG16 complex to damaged mitochondria regulates selective mitophagy to maintain cancer cell viability.

    Original languageEnglish (US)
    Article number7926
    JournalNature communications
    Volume6
    DOIs
    StatePublished - Aug 14 2015

    ASJC Scopus subject areas

    • Chemistry(all)
    • Biochemistry, Genetics and Molecular Biology(all)
    • Physics and Astronomy(all)

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  • Cite this

    Liang, J., Xu, Z. X., Ding, Z., Lu, Y., Yu, Q., Werle, K. D., Zhou, G., Park, Y. Y., Peng, G., Gambello, M. J., & Mills, G. B. (2015). Myristoylation confers noncanonical AMPK functions in autophagy selectivity and mitochondrial surveillance. Nature communications, 6, [7926]. https://doi.org/10.1038/ncomms8926