|Mitochondria as a source of mechanical signals in cardiomyocytes.|
Kaasik A, Kuum M, Joubert F, Wilding J, Ventura-Clapier R, Veksler V
Cardiovasc Res (2010)
Category: ions, mitochondria ¤ Added: Mar 22, 2010 ¤ Rating: ◊◊
AIMS: The myofibrillar and nuclear compartments in cardiomyocytes are known to be sensitive to extracellular mechanical stimuli. Recently, we have shown that alterations in the mitochondrial ionic balance in cells in situ are associated with considerably increased mitochondrial volume. Theoretically, this swelling of mitochondria could impose mechanical constraints on the myofibrils and nuclei in their vicinity. Thus, we studied whether modulation of mitochondrial volume in cardiomyocytes in situ has a mechanical effect on the myofibrillar and nuclear compartments. METHODS AND RESULTS: We used the measurement of passive force developed by saponin-permeabilized mouse ventricular fibres as a sensor for compression of the myofibrils. Osmotic compression induced by dextran caused an increase in passive force. Similarly, mitochondrial swelling induced by drugs that alter ionic homeostasis (alamethicin and propranolol) markedly augmented passive force (confirmed by confocal microscopy). Diazoxide, a mitochondrial ATP-sensitive potassium channel opener known to cause moderate mitochondrial swelling, also increased passive force (by 28 +/- 5% at 10% stretch, P < 0.01). This effect was completely blocked by 5-hydroxydecanoate (5-HD), a putative specific inhibitor of these channels. Mitochondrial swelling induced by alamethicin and propranolol led to significant nuclear deformation, which was visualized by confocal microscopy. Furthermore, diazoxide decreased nuclear volume, calculated using three-dimensional reconstructed images, in a 5-HD-dependent manner by 12 +/- 2% (P < 0.05). This corresponds to an increase in intracellular pressure of 2.1 +/- 0.3 kPa. CONCLUSION: This study is the first to demonstrate that mitochondria are able to generate internal pressure, which can mechanically affect the morphological and functional properties of intracellular organelles.