title: The mitochondrion as a key regulator of ischaemic tolerance and injury.
abstract: Vascular pathologies pose a significant health problem because of their wide prevalence and high impact on the rate of mortality. Blockade of blood flow in major blood vessels leads to ischaemia associated with oxidative stress, where mitochondria act as a major source of reactive oxygen species (ROS). While low levels of ROS perform a necessary function in normal cellular signalling and metabolism, elevated levels under pathological conditions are detrimental both at the cell and organ level. While cellular oxygenation is necessary to maintain tissue viability, a key pathological occurrence when restoring blood flow to ischaemic tissues is the subsequent burst of ROS generation following reoxygenation, resulting in a cascade of ROS-induced ROS release. This oxygen 'paradox' is a constraint in clinical practice, that is, the need for rapid and maximal restoration of blood flow while at the same time minimising the harmful impact of reperfusion injury on damaged tissues. Mitochondria play a central role in many signalling pathways, including cardioprotection against ischaemic injury and ROS signalling, thus the main target of any anti-ischaemic protective or post-injury therapeutic strategy should include mitochondria. At present, one of the most effective strategies that provide mitochondrial tolerance to ischaemia is ischaemic preconditioning. In addition, pharmacological preconditioning which mimics intrinsic natural protective mechanisms has proven effective at priming biological mechanisms to confront ischaemic damage. This review will discuss the role of mitochondria in contributing to acute ischaemia-reperfusion (IR) injury, and mechanisms of cardioprotection in respect to mitochondrial signalling pathways.
authors.affiliation: A. N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russian Federation.
authors.forename: Denis N
authors.initials: DN
authors.lastname: Silachev
authors.affiliation: A. N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russian Federation.
authors.forename: Egor Y
authors.initials: EY
authors.lastname: Plotnikov
authors.affiliation: Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, Russian Federation.
authors.forename: Irina B
authors.initials: IB
authors.lastname: Pevzner
authors.affiliation: International Laser Center, Lomonosov Moscow State University, Moscow, Russian Federation.
authors.forename: Ljubava D
authors.initials: LD
authors.lastname: Zorova
authors.affiliation: Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, Russian Federation; Research Center of Obstetrics, Gynecology and Perinatology, Moscow, Russian Federation.
authors.forename: Valentina A
authors.initials: VA
authors.lastname: Babenko
authors.affiliation: Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, Russian Federation.
authors.forename: Savva D
authors.initials: SD
authors.lastname: Zorov
authors.affiliation: Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, Russian Federation.
authors.forename: Vasily A
authors.initials: VA
authors.lastname: Popkov
authors.affiliation: Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, Russian Federation.
authors.forename: Stanislovas S
authors.initials: SS
authors.lastname: Jankauskas
authors.affiliation: Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, Russian Federation.
authors.forename: Valery P
authors.initials: VP
authors.lastname: Zinchenko
authors.affiliation: Research Center of Obstetrics, Gynecology and Perinatology, Moscow, Russian Federation.
authors.forename: Gennady T
authors.initials: GT
authors.lastname: Sukhikh
authors.affiliation: A. N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russian Federation. Electronic address: zorov@genebee.msu.su.
authors.forename: Dmitry B
authors.initials: DB
authors.lastname: Zorov
mesh_terms: D006801:Humans; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008929:Mitochondria, Heart / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D017382:Reactive Oxygen Species
keywords: Antioxidants; Brain; Heart; Kidney; Preconditioning; Reperfusion