title: The impact of cardiac ischemia/reperfusion on the mitochondria-cytoskeleton interactions.
abstract: Cardiac ischemia-reperfusion (IR) injury compromises mitochondrial oxidative phosphorylation (OxPhos) and compartmentalized intracellular energy transfer via the phosphocreatine/creatine kinase (CK) network. The restriction of ATP/ADP diffusion at the level of the mitochondrial outer membrane (MOM) is an essential element of compartmentalized energy transfer. In adult cardiomyocytes, the MOM permeability to ADP is regulated by the interaction of voltage-dependent anion channel with cytoskeletal proteins, particularly with β tubulin II. The IR-injury alters the expression and the intracellular arrangement of cytoskeletal proteins. The objective of the present study was to investigate the impact of IR on the intracellular arrangement of β tubulin II and its effect on the regulation of mitochondrial respiration. Perfused rat hearts were subjected to total ischemia (for 20min (I20) and 45min (I45)) or to ischemia followed by 30min of reperfusion (I20R and I45R groups). High resolution respirometry and fluorescent confocal microscopy were used to study respiration, β tubulin II and mitochondrial arrangements in cardiac fibers. The results of these experiments evidence a heterogeneous response of mitochondria to IR-induced damage. Moreover, the intracellular rearrangement of β tubulin II, which in the control group colocalized with mitochondria, was associated with increased apparent affinity of OxPhos for ADP, decreased regulation of respiration by creatine without altering mitochondrial CK activity and the ratio between octameric to dimeric isoenzymes. The results of this study allow us to highlight changes of mitochondrial interactions with cytoskeleton as one of the possible mechanisms underlying cardiac IR injury.
authors.affiliation: University Grenoble Alpes, Laboratory of Fundamental and Applied Bioenergetics, INSERM U1055, Grenoble, France; University Grenoble Alpes, TIMC-IMAG, CNRS, UMR5525, Grenoble, France.
authors.forename: Rafaela
authors.initials: R
authors.lastname: Bagur
authors.affiliation: University Grenoble Alpes, TIMC-IMAG, CNRS, UMR5525, Grenoble, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Tanguy
authors.affiliation: University Grenoble Alpes, Laboratory of Fundamental and Applied Bioenergetics, INSERM U1055, Grenoble, France.
authors.forename: Sarah
authors.initials: S
authors.lastname: Foriel
authors.affiliation: University Grenoble Alpes, Life Science Imaging - In Vitro Platform, IAB, INSERM CRI U823, Grenoble, France.
authors.forename: Alexei
authors.initials: A
authors.lastname: Grichine
authors.affiliation: University Grenoble Alpes, TIMC-IMAG, CNRS, UMR5525, Grenoble, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Sanchez
authors.affiliation: INSERM, U836, F-38000, Grenoble, France; University Grenoble Alpes, GIN, F-38000 Grenoble, France.
authors.forename: Karin
authors.initials: K
authors.lastname: Pernet-Gallay
authors.affiliation: National Institute of Chemical Physics and Biophysics, Laboratory of Bioenergetics, Tallinn, Estonia.
authors.forename: Tuuli
authors.initials: T
authors.lastname: Kaambre
authors.affiliation: Innsbruck Medical University, Cardiac Surgery Research Laboratory, Innsbruck A-6020, Austria.
authors.forename: Andrey V
authors.initials: AV
authors.lastname: Kuznetsov
authors.affiliation: University Grenoble Alpes, TIMC-IMAG, CNRS, UMR5525, Grenoble, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Usson
authors.affiliation: University Grenoble Alpes, TIMC-IMAG, CNRS, UMR5525, Grenoble, France.
authors.forename: François
authors.initials: F
authors.lastname: Boucher
authors.affiliation: University Grenoble Alpes, Laboratory of Fundamental and Applied Bioenergetics, INSERM U1055, Grenoble, France; Hospital of the University Grenoble Alpes, Department Thorax (EFCR), France. Electronic address: rita.guzun@gmail.com.
authors.forename: Rita
authors.initials: R
authors.lastname: Guzun
mesh_terms: D000818:Animals; D019069:Cell Respiration; D003599:Cytoskeleton / Q000378:metabolism / Q000473:pathology*; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism / Q000473:pathology*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D017208:Rats, Wistar; D014404:Tubulin / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D014404:Tubulin
keywords: Heart; Ischemia/reperfusion; Mitochondria; Respiration; Tubulin