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HK2/hexokinase-II integrates glycolysis and autophagy to confer cellular protection

Valerie P Tan1, Shigeki Miyamoto

  • 1a Department of Pharmacology ; University of California ; San Diego; La Jolla , CA USA.

Autophagy
|June 16, 2015
PubMed

Insights

Hexokinase-II (HK2) acts as a metabolic switch, activating autophagy during glucose deprivation to protect heart cells and maintain energy balance. This discovery links glucose metabolism directly to cellular survival pathways.

Area of Science:

  • Cellular metabolism
  • Molecular biology
  • Autophagy research

Background:

  • Hexokinases (HKs) initiate glucose metabolism by phosphorylating glucose to glucose 6-phosphate (G6P).
  • Hexokinase-II (HK2) is a key isoform in vital tissues and is upregulated in cancers exhibiting the Warburg effect.
  • HK2's role extends beyond glycolysis to cell survival, with its link to autophagy being unclear.

Purpose of the Study:

  • To elucidate the molecular link between cellular metabolism and autophagic pathways.
  • To investigate the role of Hexokinase-II (HK2) in regulating autophagy under glucose-deprived conditions.
  • To understand how HK2 ensures cellular energy homeostasis during starvation.

Main Methods:

  • Investigated Hexokinase-II (HK2) function in cardiomyocytes.
  • Analyzed the response to glucose deprivation (HK substrate deprivation).
  • Examined the interplay between glycolysis and autophagy.

Main Results:

  • Hexokinase-II (HK2) was found to facilitate autophagy in response to glucose deprivation in cardiomyocytes.
  • HK2 acts as a molecular switch, shifting from glycolysis to autophagy.
  • This switch is crucial for protecting cardiomyocytes and maintaining energy homeostasis under starvation.

Conclusions:

  • Hexokinase-II (HK2) plays a critical role in linking glucose metabolism to autophagy.
  • HK2 functions as a protective mechanism in cardiomyocytes during nutrient scarcity.
  • The findings highlight HK2's dual role in metabolism and cell survival via autophagy.
Keywords:
MTORC1autophagyglucose 6-phosphateglycolysishexokinase-II

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