title: Hexokinases and cardioprotection.
abstract: As mediators of the first enzymatic step in glucose metabolism, hexokinases (HKs) orchestrate a variety of catabolic and anabolic uses of glucose, regulate antioxidant power by generating NADPH for glutathione reduction, and modulate cell death processes by directly interacting with the voltage-dependent anion channel (VDAC), a regulatory component of the mitochondrial permeability transition pore (mPTP). Here we summarize the current state-of-knowledge about HKs and their role in protecting the heart from ischemia/reperfusion (I/R) injury, reviewing: 1) the properties of different HK isoforms and how their function is regulated by their subcellular localization; 2) how HKs modulate glucose metabolism and energy production during I/R; 3) the molecular mechanisms by which HKs influence mPTP opening and cellular injury during I/R; and 4) how different metabolic and HK profiles correlate with susceptibility to I/R injury and cardioprotective efficacy in cancer cells, neonatal hearts, and normal, hypertrophied and failing adult hearts, and how these difference may guide novel therapeutic strategies to limit I/R injury in the heart. This article is part of a Special Issue entitled "Mitochondria: From Basic Mitochondrial Biology to Cardiovascular Disease".
authors.affiliation: UCLA Cardiovascular Research Laboratory, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA; Department of Medicine (Cardiology), David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA; Department of Physiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Calmettes
authors.affiliation: UCLA Cardiovascular Research Laboratory, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA; Department of Medicine (Cardiology), David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA; Department of Physiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
authors.forename: Bernard
authors.initials: B
authors.lastname: Ribalet
authors.affiliation: UCLA Cardiovascular Research Laboratory, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA; Department of Medicine (Cardiology), David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA; Department of Physiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: John
authors.affiliation: UCLA Cardiovascular Research Laboratory, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA; Department of Medicine (Cardiology), David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA; Department of Physiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
authors.forename: Paavo
authors.initials: P
authors.lastname: Korge
authors.affiliation: UCLA Cardiovascular Research Laboratory, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA; Department of Medicine (Cardiology), David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA; Department of Physiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
authors.forename: Peipei
authors.initials: P
authors.lastname: Ping
authors.affiliation: UCLA Cardiovascular Research Laboratory, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA; Department of Medicine (Cardiology), David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA; Department of Physiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA. Electronic address: jweiss@mednet.ucla.edu.
authors.forename: James N
authors.initials: JN
authors.lastname: Weiss
mesh_terms: D000818:Animals; D005947:Glucose / Q000378:metabolism; D006331:Heart Diseases / Q000378:metabolism; D006593:Hexokinase / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes; D055442:Metabolome; D008929:Mitochondria, Heart / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D015428:Myocardial Reperfusion Injury / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism
chemical_list: D007527:Isoenzymes; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D006593:Hexokinase; D005947:Glucose
keywords: Cardioprotection; Hexokinase; Ischemia/reperfusion; Postconditioning; Preconditioning