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 Nanoparticle Exposure Can Awaken Dormant Viruses in the Lungs
16.01.2017 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Cholera bacteria infect more effectively with a simple twist of shape
13.01.2017 | Princeton University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).

Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...

Im Focus: Bacterial Pac Man molecule snaps at sugar

Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.

The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

Water - as the underlying driver of the Earth’s carbon cycle

17.01.2017 | Earth Sciences

Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

17.01.2017 | Materials Sciences

Smart homes will “LISTEN” to your voice

17.01.2017 | Architecture and Construction

VideoLinks
B2B-VideoLinks
More VideoLinks >>>