Mitochondrial bioenergetics and cardiolipin alterations in myocardial ischemia-reperfusion injury: implications for pharmacological cardioprotection

Am J Physiol Heart Circ Physiol. 2018 Nov 1;315(5):H1341-H1352. doi: 10.1152/ajpheart.00028.2018. Epub 2018 Aug 10.

Abstract

Mitochondrial dysfunction plays a central role in myocardial ischemia-reperfusion (I/R) injury. Increased reactive oxygen species production, impaired electron transport chain activity, aberrant mitochondrial dynamics, Ca2+ overload, and opening of the mitochondrial permeability transition pore have been proposed as major contributory factors to mitochondrial dysfunction during myocardial I/R injury. Cardiolipin (CL), a mitochondria-specific phospholipid, plays a pivotal role in multiple mitochondrial bioenergetic processes, including respiration and energy conversion, in mitochondrial morphology and dynamics as well as in several steps of the apoptotic process. Changes in CL levels, species composition, and degree of oxidation may have deleterious consequences for mitochondrial function with important implications in a variety of pathophysiological conditions, including myocardial I/R injury. In this review, we focus on the role played by CL alterations in mitochondrial dysfunction in myocardial I/R injury. Pharmacological strategies to prevent myocardial injury during I/R targeting mitochondrial CL are also examined.

Keywords: cardiolipin; cardioprotection; heart ischemia-reperfusion injury; mitochondrial bioenergetics.

Publication types

  • Review

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cardiolipins / metabolism*
  • Cardiovascular Agents / therapeutic use*
  • Energy Metabolism / drug effects*
  • Humans
  • Lipid Peroxidation / drug effects
  • Mitochondria, Heart / drug effects*
  • Mitochondria, Heart / metabolism
  • Mitochondria, Heart / pathology
  • Mitochondrial Dynamics / drug effects
  • Mitochondrial Membrane Transport Proteins / drug effects
  • Mitochondrial Membrane Transport Proteins / metabolism
  • Mitochondrial Permeability Transition Pore
  • Mitophagy / drug effects
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / pathology
  • Myocardial Infarction / physiopathology
  • Myocardial Infarction / prevention & control*
  • Myocardial Reperfusion Injury / metabolism
  • Myocardial Reperfusion Injury / pathology
  • Myocardial Reperfusion Injury / physiopathology
  • Myocardial Reperfusion Injury / prevention & control*
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / metabolism
  • Myocytes, Cardiac / pathology
  • Oxidative Stress / drug effects
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects

Substances

  • Cardiolipins
  • Cardiovascular Agents
  • Mitochondrial Membrane Transport Proteins
  • Mitochondrial Permeability Transition Pore
  • Reactive Oxygen Species