Mechano-sensitivity of mitochondrial function in mouse cardiac myocytes. (November 2017)

• Record Type: Journal Article
• Authors: Iribe, Gentaro; Kaihara, Keiko; Yamaguchi, Yohei; Nakaya, Michio; Inoue, Ryuji; Naruse, Keiji
• Is Part Of: Progress in biophysics and molecular biology. Volume 130:Part B(2017)
• Page Start: 315
• Page End: 322
• Publication Date: 2017-11
• Subjects: Cardiomyocyte -- Respiratory chain -- Mitochondrial membrane potential -- Reactive oxygen species -- Carbon fibre; Biophysics -- Periodicals; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular Biology -- Periodicals; Biophysique -- Périodiques; Biochimie -- Périodiques; 571.4
• DOI: 10.1016/j.pbiomolbio.2017.05.015
• Languages: English
• ISSNs: 0079-6107

Abstract

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.