From: natashavita@earthlink.net
Date: Tue Jan 07 2003 - 10:40:50 MST
Fowarded from Pete Markiewicz:
Contact: Joanna Downer
jdowner1@jhmi.edu
410-614-5105
Johns Hopkins Medical Institutions
"Sirtuin protein has a new function; May play role in lifespan extension
Scientists from Johns Hopkins and the University of Wisconsin have
discovered that a protein called Sir2, which is found in nearly all living
cells, has a new function that might help explain how calorie restriction
can increase lifespans for some animals, the scientists say. Their report
appeared in the Dec. 20 issue of Science.
A number of laboratories have shown that restricting total calorie intake
extends the lifespans of organisms ranging from yeast to laboratory
animals. Others have shown that this effect requires Sir2's protein family,
called sirtuins, and increased cellular respiration, which is the process
of using oxygen to convert calories into energy.
Studying bacteria, the Johns Hopkins-Wisconsin team has discovered that
sirtuin controls the enzyme that converts acetate, a source of calories,
into acetyl-CoA, a key component of cellular respiration.
"Sirtuins are highly conserved across species, but this is a
never-before-described ability of the protein," says Jef Boeke, Ph.D.,
professor of molecular biology and genetics at Johns Hopkins' Institute for
Basic Biomedical Sciences. "If sirtuins modify this enzyme in other
organisms, turning on production of acetyl-CoA, it could help explain why
restricting regular sources of calories -- sugars and fats -- leads to
extended lifespan in many kinds of organisms."
Identified in all living creatures, including single-celled organisms like
bacteria and yeast, sirtuin proteins previously were known to play an
important role in keeping regions of chromosomes turned off. By modifying
the histone proteins that keep DNA tightly coiled, sirtuins prevent certain
regions of chromosomes from being exposed to cells' DNA-reading machinery.
Sirtuin's new role in bacteria involves the same modification as its
interaction with histone -- removing an acetyl group, a "decoration" added
to a protein's sequence (like phosphate) -- but the targeted protein is
involved in producing energy, not controlling chromosomes.
Normally, cells can survive by using many different molecules as sources of
energy -- potent sources like fats or sugars, or even relatively
energy-poor molecules like acetate.
However, Jorge Escalante-Semerena and Vincent Starai of the University of
Wisconsin created a strain of bacteria missing its sirtuin protein and
noticed that it couldn't live on acetate. Boeke had previously noticed that
yeast without sirtuin had the same problem, so the researchers dug deeper.
They discovered that the sirtuin protein in bacteria is a crucial modifier
of an enzyme known as acetyl-CoA synthetase, which converts acetate into
acetyl-CoA in a two-step process. Acetyl-CoA then can directly fuel the
citric acid cycle, the central energy-producing step in cellular
respiration.
"This is a completely new target for the sirtuin protein," says Boeke, who
has been studying "transcriptional silencing" -- sirtuin's previously known
role -- for some time. "Converting acetate isn't the cell's only way of
making acetyl-CoA, but when acetate is the major energy source, it's
crucial. Now we have to check for this role in other organisms."
The Wisconsin researchers found that sirtuin activates the first step of
acetate's conversion, and Boeke and Johns Hopkins' Robert Cole and Ivana
Celic figured out that sirtuin does so by removing an acetyl group from a
lysine in the enzyme's active site.
While bacteria and yeast are both single-celled critters, yeast are much
more closely related to animals, including humans, than are bacteria. If
the yeast version of sirtuin also modifies the newly identified target,
that would more likely reflect the protein's role in animals and would more
formally link the protein to lifespan extension, at least for yeast. The
effect of calorie restriction on the lifespan of bacteria has not been
established.
###
The studies were funded by the National Institutes of Health, and the
Jerome Stefaniak and Pfizer Predoctoral Fellowships (to Starai). The Johns
Hopkins Mass Spectrometry facility is funded by the National Center for
Research Resources, the Johns Hopkins Fund for Medical Discovery, and the
Johns Hopkins Institute for Cell Engineering. Authors on the paper are
Starai and Escalante-Semerena of Wisconsin; and Celic, Cole and Boeke of
the Johns Hopkins School of Medicine.
On the Web: http://www.sciencemag.org
Johns Hopkins Medical Institutions' news releases are available on an
EMBARGOED basis on EurekAlert at http://www.eurekalert.org, and from the
Office of Communications and Public Affairs' direct e-mail news release
service. To enroll, call 410-955-4288 or send e-mail to bsimpkins@jhmi.edu.
On a POST-EMBARGOED basis find them at http://www.hopkinsmedicine.org"
Joanna Downer
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