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 Mills

Research output: Contribution to journalArticle

41 Citations (Scopus)

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
Externally publishedYes

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adenosine monophosphate
AMP-Activated Protein Kinases
Autophagy
surveillance
selectivity
Mitochondrial Degradation
proteins
Mitochondria
mitochondria
Cell Survival
Cells
damage
viability
Energy Metabolism
induction
cancer

ASJC Scopus subject areas

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

Cite this

Myristoylation confers noncanonical AMPK functions in autophagy selectivity and mitochondrial surveillance. / Liang, Jiyong; Xu, Zhi Xiang; Ding, Zhiyong; Lu, Yiling; Yu, Qinghua; Werle, Kaitlin D.; Zhou, Ge; Park, Yun Yong; Peng, Guang; Gambello, Michael J.; Mills, Gordon.

In: Nature Communications, Vol. 6, 7926, 14.08.2015.

Research output: Contribution to journalArticle

Liang, J, Xu, ZX, Ding, Z, Lu, Y, Yu, Q, Werle, KD, Zhou, G, Park, YY, Peng, G, Gambello, MJ & Mills, G 2015, 'Myristoylation confers noncanonical AMPK functions in autophagy selectivity and mitochondrial surveillance', Nature Communications, vol. 6, 7926. https://doi.org/10.1038/ncomms8926
Liang, Jiyong ; Xu, Zhi Xiang ; Ding, Zhiyong ; Lu, Yiling ; Yu, Qinghua ; Werle, Kaitlin D. ; Zhou, Ge ; Park, Yun Yong ; Peng, Guang ; Gambello, Michael J. ; Mills, Gordon. / Myristoylation confers noncanonical AMPK functions in autophagy selectivity and mitochondrial surveillance. In: Nature Communications. 2015 ; Vol. 6.
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