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Myristoylation confers noncanonical AMPK functions in autophagy selectivity and mitochondrial surveillance

Author

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  • Jiyong Liang

    (The University of Texas MD Anderson Cancer Center)

  • Zhi-Xiang Xu

    (Comprehensive Cancer Center, University of Alabama at Birmingham
    Key Laboratory of Pathobiology, Ministry of Education, Norman Bethune College of Medicine, Jilin University)

  • Zhiyong Ding

    (The University of Texas MD Anderson Cancer Center)

  • Yiling Lu

    (The University of Texas MD Anderson Cancer Center)

  • Qinghua Yu

    (The University of Texas MD Anderson Cancer Center)

  • Kaitlin D. Werle

    (Comprehensive Cancer Center, University of Alabama at Birmingham)

  • Ge Zhou

    (The University of Texas MD Anderson Cancer Center)

  • Yun-Yong Park

    (The University of Texas MD Anderson Cancer Center
    Present addresses: Department of Medicine, ASAN Institute for Life Sciences, ASAN Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Korea.)

  • Guang Peng

    (The University of Texas MD Anderson Cancer Center)

  • Michael J. Gambello

    (University of Texas Health Science Center at Houston
    Present addresses: Emory University School of Medicine, 615 Clifton Road, Atlanta, Georgia 30322, USA.)

  • Gordon B. Mills

    (The University of Texas MD Anderson Cancer Center)

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.

Suggested Citation

  • 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, 2015. "Myristoylation confers noncanonical AMPK functions in autophagy selectivity and mitochondrial surveillance," Nature Communications, Nature, vol. 6(1), pages 1-14, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8926
    DOI: 10.1038/ncomms8926
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