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Study of Protein-protein Interactions in Autophagy Research
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Study of Protein-protein Interactions in Autophagy Research

Published on: September 9, 2017

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Myristoylation confers noncanonical AMPK functions in autophagy selectivity and mitochondrial surveillance

Jiyong Liang1, Zhi-Xiang Xu2, Zhiyong Ding1

  • 1Department of Systems Biology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.

Nature Communications
|August 15, 2015
PubMed

Insights

AMP-activated protein kinase (AMPK) is crucial for mitophagy, the process of clearing damaged mitochondria. Its recruitment to damaged mitochondria by NMT1 promotes cell survival in cancer.

Area of Science:

  • Cellular bioenergetics and mitochondrial quality control.
  • Molecular mechanisms of mitophagy.
  • Cancer cell survival pathways.

Background:

  • AMP-activated protein kinase (AMPK) is a key energy sensor.
  • The role of AMPK in mitochondrial damage surveillance and mitophagy is not well understood.
  • Mitochondrial dysfunction is implicated in various diseases, including cancer.

Purpose of the Study:

  • To investigate the role of AMPK in mitophagy.
  • To elucidate the molecular mechanisms by which AMPK regulates mitophagy.
  • To determine if AMPK targeting to mitochondria impacts cancer cell viability.

Main Methods:

  • Investigated the physical association of AMPK with mitophagy-related proteins (ATG16-ATG5-12, VPS34 complex).
  • Examined the recruitment of AMPK to damaged mitochondria.
  • Assessed the effect of targeting AMPK to mitochondria on mitophagy and cell survival.
  • Studied the role of N-myristoylation by NMT1 in AMPK recruitment.

Main Results:

  • AMPK is required for efficient mitophagy.
  • Mitochondrial damage induces AMPK association with ATG16-ATG5-12 and recruitment of VPS34/ATG16 complexes.
  • Targeting AMPK to mitochondria induces mitophagy and promotes cancer cell survival.
  • N-myristoylation of AMPKβ by NMT1 is essential for AMPK recruitment to mitochondria.

Conclusions:

  • AMPK plays a critical role in regulating mitophagy.
  • A spatiotemporal model is proposed where AMPK recruitment to damaged mitochondria, via NMT1, initiates selective mitophagy.
  • This AMPK-mediated mitophagy pathway is vital for maintaining cancer cell viability.

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