Mechano-sensitivity of mitochondrial function in mouse cardiac myocytes

Gentaro Iribe, Keiko Kaihara, Yohei Yamaguchi, Michio Nakaya, Ryuji Inoue, Keiji Naruse

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5 Citations (Scopus)

Abstract

Mitochondria are an important source of reactive oxygen species (ROS). Although it has been reported that myocardial stretch increases cellular ROS production by activating nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2), referred to as X-ROS signalling, the involvement of mitochondria in X-ROS is not clear. Mitochondria are organelles that generate adenosine triphosphate (ATP) for cellular energy needs, which are mechanical-load-dependent. Therefore, it would not be surprising if these organelles had mechano-sensitive functions associated with stretch-induced ROS production. In the present study, we investigated the relation between X-ROS and mitochondrial stretch-sensitive responses in isolated mouse cardiac myocytes. The cells were subjected to 10% axial stretch using computer-controlled, piezo-manipulated carbon fibres attached to both cell ends. Cellular ROS production and mitochondrial membrane potential (δψm) were assessed optically by confocal microscopy. The axial stretch increased ROS production and hyperpolarised δψm. Treatment with a mitochondrial metabolic uncoupler, carbonyl cyanide-p-trifluoromethoxyphenylhydrazone (FCCP), at 0.5 μM did not suppress stretch-induced ROS production, whereas treatment with a respiratory Complex III inhibitor, antimycin A (5 μM), blunted the response. Although NOX inhibition by apocynin abrogated the stretch-induced ROS production, it did not suppress stretch-induced hyperpolarisation of δψm. These results suggest that stretch causes activation of the respiratory chain to hyperpolarise δψm, followed by NOX activation, which increases ROS production.

Original languageEnglish
JournalProgress in Biophysics and Molecular Biology
DOIs
Publication statusAccepted/In press - 2017

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Keywords

  • Carbon fibre
  • Cardiomyocyte
  • Mitochondrial membrane potential
  • Reactive oxygen species
  • Respiratory chain

ASJC Scopus subject areas

  • Biophysics
  • Molecular Biology

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