Regulation of AMPK by the ubiquitin proteasome system

Makhosazane Zungu, Jonathan C. Schisler, M. Faadiel Essop, Chris McCudden, Cam Patterson, Monte Willis

Research output: Contribution to journalReview article

36 Citations (Scopus)

Abstract

The 5′-AMP-activated protein kinase (AMPK) functions as a metabolic fuel gauge that is activated in response to environmental stressors to restore cellular energy balance. In the heart, AMPK coordinates the activation of glucose and fatty acid metabolic pathways to ensure increased production of myocardial ATP when required, such as during cardiac ischemia/reperfusion and hypertrophy, causing an increase in AMPK activity that can be viewed as both protective and maladaptive. While we understand the basic regulation of AMPK activity by kinases, recent studies have introduced the concept that AMPK is regulated by other post-translational modifications, specifically ubiquitination. These studies reported that the ubiquitin ligase cell death-inducing DFFA-like effector a ubiquitinates the β subunit of AMPK to regulate its steady-state protein levels. Other investigators found that AMPK regulatory components, including the AMPK α subunit and AMPK kinases NUAK1 and MARK4, can be ubiquitinated with atypical ubiquitin chains. The USP9X-deubiquitinating enzyme was identified to remove ubiquitination from both NUAK1 and MARK4. Lastly, AMPK activation increases the expression of the ubiquitin ligases MAFBx/Atrogin-1 and MuRF1. These ubiquitin ligases regulate key cardiac transcription factors to control cardiomyocyte mass and remodeling, thus suggesting another mechanism by which AMPK may function in the heart. The relevance of AMPK ubiquitination in cardiac disease has yet to be tested directly, but it likely represents an important mechanism that occurs in common cardiac diseases that may be targeted for therapy.

Original languageEnglish (US)
Pages (from-to)4-11
Number of pages8
JournalAmerican Journal of Pathology
Volume178
Issue number1
DOIs
StatePublished - Jan 1 2011
Externally publishedYes

Fingerprint

AMP-Activated Protein Kinases
Proteasome Endopeptidase Complex
Ubiquitin
Ubiquitination
Ligases
Heart Diseases
Protein Subunits
Post Translational Protein Processing
Metabolic Networks and Pathways
Cardiac Myocytes
Hypertrophy
Reperfusion
Cell Death
Transcription Factors
Fatty Acids
Ischemia
Adenosine Triphosphate
Research Personnel

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Zungu, M., Schisler, J. C., Essop, M. F., McCudden, C., Patterson, C., & Willis, M. (2011). Regulation of AMPK by the ubiquitin proteasome system. American Journal of Pathology, 178(1), 4-11. https://doi.org/10.1016/j.ajpath.2010.11.030

Regulation of AMPK by the ubiquitin proteasome system. / Zungu, Makhosazane; Schisler, Jonathan C.; Essop, M. Faadiel; McCudden, Chris; Patterson, Cam; Willis, Monte.

In: American Journal of Pathology, Vol. 178, No. 1, 01.01.2011, p. 4-11.

Research output: Contribution to journalReview article

Zungu, M, Schisler, JC, Essop, MF, McCudden, C, Patterson, C & Willis, M 2011, 'Regulation of AMPK by the ubiquitin proteasome system', American Journal of Pathology, vol. 178, no. 1, pp. 4-11. https://doi.org/10.1016/j.ajpath.2010.11.030
Zungu, Makhosazane ; Schisler, Jonathan C. ; Essop, M. Faadiel ; McCudden, Chris ; Patterson, Cam ; Willis, Monte. / Regulation of AMPK by the ubiquitin proteasome system. In: American Journal of Pathology. 2011 ; Vol. 178, No. 1. pp. 4-11.
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