Role of AMPK in regulation of LC3 lipidation as a marker of autophagy in skeletal muscle

Andreas Mæchel Fritzen, Christian Frøsig, Jacob Jeppesen, Thomas Elbenhardt Jensen, Anne Marie Lundsgaard, Annette Karen Serup, Peter Schjerling, Christopher Proud, Erik A. Richter, Bente Kiens

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41 Citations (Scopus)

Abstract

During induction of the autophagosomal degradation process, LC3-I is lipidated to LC3-II and associates to the cargo isolation membrane allowing for autophagosome formation. Lipidation of LC3 results in an increased LC3-II/LC3-I ratio, and this ratio is an often used marker for autophagy in various tissues, including skeletal muscle. From cell studies AMPK has been proposed to be necessary and sufficient for LC3 lipidation. The aim of the present study was to investigate the role of AMPK in regulation of LC3 lipidation as a marker of autophagy in skeletal muscle. We observed an increase in the LC3-II/LC3-I ratio in skeletal muscle of AMPKα2 kinase-dead (KD) (p < 0.001) and wild type (WT) (p < 0.05) mice after 12 h of fasting, which was greater (p < 0.05) in AMPKα2 KD mice than in WT. The fasting-induced increase in the LC3-II/LC3-I ratio in both genotypes coincided with an initial decrease (p < 0.01) in plasma insulin concentration, a subsequent decrease in muscle mTORC1 signaling and increased (p < 0.05) levels of the autophagy-promoting proteins, FoxO3a and ULK1. Furthermore, a higher (p < 0.01) LC3-II/LC3-I ratio was observed in old compared to young mice. We were not able to detect any change in LC3 lipidation with either in vivo treadmill exercise or in situ contractions. Collectively, these findings suggest that AMPKα2 is not necessary for induction of LC3 lipidation with fasting and aging. Furthermore, LC3 lipidation is increased in muscle lacking functional AMPKα2 during fasting and aging. Moreover, LC3 lipidation seems not to be a universal response to muscle contraction in mice.

Original languageEnglish
Pages (from-to)663-674
Number of pages12
JournalCellular Signalling
Volume28
Issue number6
DOIs
Publication statusPublished - 1 Jun 2016

Keywords

  • AMPK
  • Aging
  • Autophagy
  • Exercise and eEF2K
  • Fasting
  • LC3 lipidation

ASJC Scopus subject areas

  • Cell Biology

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