Estonian-French Team
Demonstrates First Direct Mechanical Communication Between Mitochondria And
Cardiomyocyte Nucleus
SAN FRANCISCO (April 3, 2006) – 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.
*Presentations: The paper, “Direct
mechanical communication between mitochondria and nucleus in cardiac cells,”
was chosen to be part of the “Physiological Genomics of Skeletal Muscle
Adaptation in Health and Disease” Featured Topic session 199, sponsored by
the APS Muscle Biology Group. Sunday April 2 at 10:30 a.m. in the
Convention Center, Room 130, Moscone North. The paper will be presented at
11:15 a.m.
The research also will be presented 12:30-3 p.m.
Monday April 3, APS Physiology Signaling in muscle session 486.6/board
#C732. Research was performed by Allen Kaasik, Department of
Pharmacology, University of Tartu, Estonia, who collaborates with Renée
Ventura-Clapier and Vladimir Veksler of INSERM, University of Paris-Sud,
France.
Health
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% ± 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.”
Next steps
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.
Funding: Research was supported by Egide, a
French government short-term travel program and by INSERM, the French
government health institute.
* * *
Editor’s Note: For
further information or to schedule an interview with a member of
the research team, please contact Donna Krupa at the APS newsroom @
415.905.1024 (March 31-April 5); or (703) 967-2751 (cell) or (301) 634-7209
(office),
dkrupa@the-aps.org; or Christine Guilfoy at 978.290.2400 (cell) or
301.634.7253 (office).
A searchable
online program for EB is at
http://www.faseb.org/meetings/eb2006/call/default.htm
# # #
The
American Physiological Society was founded in 1887 to foster basic and
applied bioscience. The Bethesda, Maryland-based society has more than
10,500 members and publishes 14 peer-reviewed journals containing almost
4,000 articles annually.
APS
provides a wide range of research, educational and career support and
programming to further the contributions of physiology to understanding the
mechanisms of diseased and healthy states. In May 2004, APS received
the Presidential Award for Excellence in Science,
Mathematics and Engineering Mentoring (PAESMEM).
Experimental Biology is an annual
scientific meeting convened by the Federation of American Societies of
Experimental Biology, including the American Physiological Society (APS)
and other biomedical societies. The meeting features “nominated” lectures,
symposia, research presentations, awards, a job placement center, and an
exhibit of scientific equipment, supplies, and publications. This year’s
participating Societies are APS, American Association of
Anatomists, American Society for Biochemistry and Molecular Biology,
American Society for Investigative Pathology, American Society for
Nutritional Sciences, and the American Society for Pharmacology and
Experimental Therapeutics.
