Mitochondria induce nuclear deformation

In a paper being presented in two American Physiological Society sessions at Experimental Biology 2006, a joint Estonian-French team demonstrated "for the first time that mitochondria are able to induce nuclear deformation, suggesting that mitochondria may mechanically regulate nuclear function."

The team, which has been collaborating for over 10 years, reported that it recently "found a very interesting and unexpected phenomenon: various substances which increase mitochondrial size, also increased contractile force of cardiac fibers," or myofibrils. This effect isn't related to the mitochondrial energy production, they noted, and so a hypothesis was developed that "there might be in cardiac cells some form of mechanical signaling between organelles."

Vladimir Veksler, a former Soviet scientist who maintained his contacts with Estonian researchers after moving to Paris, said their latest research "shows that substances increasing the mitochondria can also compress the nuclear organelles, ensuring storage and treatment of genetic information."

Taken together, the results indicate that "the existence of such mechanical signaling between mitochondria and myofibrils opens a new possibility to search for drugs capable of increasing cardiac contractility," Veksler said.

Veksler said the team has been interested for many years in mechanisms of interaction between mitochondria and other organelles. They use "skinned cardiac fibers" whose outer membranes have been chemically removed which allows them to control the intracellular medium. They believed that in the tightly packed myocyte, that "mitochondria could push and compress nearby structures like myofibrils and modulate their functional properties."

This additional evidence of intracellular mechanical signaling "may have important physiological significance," Veksler said. He noted that a "number of studies indicate a sensitivity of nuclei to external mechanical forces and suggest that nuclear deformation could influence gene expression processes. Thus, we hypothesize that drugs or intracellular conditions inducing mitochrondrial swelling could by mechanical means influence gene expression.

"More studies are needed to explore this very intriguing and promising field of knowledge," he concluded.

In the experiment, the researchers found that in an artificial medium mimicking the cytosol, 10 micro-molar of valinomycin (a potassium ionophore that induces mitochondrial matrix swelling) decreased nuclear volume by a significant 12% 1 2%. And 150 micro-molar of diazoxide (a mitochondrial ATP-sensitive potassium channel opener) reduced nuclear volume a similar amount. "However, 150 micro-molar of 5-hydrooxydecanoate (thought to be a specific inhibitor of these channels), completely blocked the effect," according to the report, leading to the conclusion that: "mitochondria are able to induce nuclear deformation, suggesting that mitochondria may mechanically regulate nuclear function."

Veksler said one idea that needs to be checked out is: If this mechanical communication changes nuclear geometry, does it also impact nuclear function, namely transcription?

Indeed, he said one reason for presenting their findings at Experimental Biology is to find collaborators interested in studying the relevant transcriptional processes.

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