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Direct mechanical communication between mitochondria and nucleus in cardiac cells
Author(s) -
Kaasik Allen,
VenturaClapier Renée,
Veksler Vladimir
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a819
Subject(s) - mitochondrion , mitochondrial matrix , cytosol , biophysics , chemistry , nucleus , potassium channel , propidium iodide , antimycin a , diazoxide , microbiology and biotechnology , adenine nucleotide translocator , biochemistry , biology , programmed cell death , apoptosis , endocrinology , insulin , enzyme
Extracellular forces, which deform the cell and thereby its nucleus, are thought to be able to modulate nuclear functions. However, mechanical signals may also arise from within the cell. We have recently shown (Kaasik et al. FASEB J. 2004, 18, 1219) that mitochondrial modulators, which increase the matrix volume, augment force developed by permeabilized ventricular fibers, due to physical compression of the myofibrillar compartment by swollen mitochondria. In the present study we investigated whether mitochondrial modulators that induce matrix swelling were able to affect nuclear shape and volume by imposing mechanical constraints. Nuclei in rat saponin‐permeabilized cardiomyocytes were stained with propidium iodide and analyzed by confocal microscopy after image deconvolution and 3D reconstruction. In an artificial medium mimicking the cytosol, 10 μM valinomycin (a potassium ionophore, inducing mitochondrial matrix swelling) decreased nuclear volume by 12 ± 2% (p<0.001). This effect was not related to inhibition of ATP‐generating activity as bongkrekic acid (adenine nucleotide translocator blocker), which did not alter matrix volume, had no effect on nuclei. Furthermore, 150 μM diazoxide, a mitochondrial ATP‐sensitive potassium channel opener, also reduced nuclear volume by 12 ± 2% (p=0.001) whereas 150 μM 5‐hydroxydecanoate, thought to be a specific inhibitor of these channels, completely blocked the effect. Thus, we have shown for the first time that mitochondria are able to induce nuclear deformation, suggesting that mitochondria may mechanically regulate nuclear function.