Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Sirtuin protein has a new function; May play role in lifespan extension

07.01.2003


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.

Joanna Downer | EurekAlert!
Further information:
http://www.hopkinsmedicine.org

More articles from Life Sciences:

nachricht When Air is in Short Supply - Shedding light on plant stress reactions when oxygen runs short
23.03.2017 | Institut für Pflanzenbiochemie

nachricht WPI team grows heart tissue on spinach leaves
23.03.2017 | Worcester Polytechnic Institute

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

When Air is in Short Supply - Shedding light on plant stress reactions when oxygen runs short

23.03.2017 | Life Sciences

Researchers use light to remotely control curvature of plastics

23.03.2017 | Power and Electrical Engineering

Sea ice extent sinks to record lows at both poles

23.03.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>