Role of YAP/TAZ in Energy Metabolism in the Heart

J Cardiovasc Pharmacol. 2019 Dec;74(6):483-490. doi: 10.1097/FJC.0000000000000736.

Abstract

The heart requires a high amount of energy, in the form of adenosine triphosphate, to maintain its viability and pump function. Anaerobic glycolysis and mitochondrial oxidative phosphorylation are the two main metabolic pathways by which adenosine triphosphate is generated, using fatty acids, glucose, lactate, and ketone bodies as primary substrates. Previous studies have demonstrated that, in response to stress, the heart undergoes alterations in metabolism, ranging from changes in substrate utilization to mitochondrial function, collectively called metabolic remodeling. However, the molecular mechanism mediating metabolic remodeling in the heart remains unclear. Yes-associated protein 1 (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), which are major downstream effectors of the Hippo signaling pathway, play an important role in the regulation of heart size and cellular homeostasis of cardiomyocytes through the regulation of various transcriptional factors under both physiological and pathophysiological conditions. Recent findings in various organs and cell types have revealed that YAP and TAZ play an important role in energy metabolism. Here, we summarize what is currently known about YAP/TAZ in the regulation of metabolism of various substrates and mitochondrial function in various organs and cell types and discuss the potential role of YAP/TAZ in mediating metabolic remodeling of the heart during stress and heart failure.

Publication types

  • Review

MeSH terms

  • Adaptation, Physiological
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Energy Metabolism*
  • Heart Failure / metabolism*
  • Heart Failure / pathology
  • Heart Failure / physiopathology
  • Hippo Signaling Pathway
  • Humans
  • Mitochondria, Heart / metabolism*
  • Mitochondria, Heart / pathology
  • Myocardium / metabolism*
  • Myocardium / pathology
  • Phosphorylation
  • Protein Serine-Threonine Kinases / metabolism
  • Signal Transduction
  • Trans-Activators / metabolism*
  • Transcription Factors / metabolism*
  • Transcriptional Coactivator with PDZ-Binding Motif Proteins
  • YAP-Signaling Proteins

Substances

  • Adaptor Proteins, Signal Transducing
  • Trans-Activators
  • Transcription Factors
  • Transcriptional Coactivator with PDZ-Binding Motif Proteins
  • WWTR1 protein, human
  • YAP-Signaling Proteins
  • YAP1 protein, human
  • Protein Serine-Threonine Kinases