Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

How Old Yeast Cells Send Off Their Daughter Cells without the Baggage of Old Age

28.11.2011
The accumulation of damaged protein is a hallmark of aging that not even the humble baker’s yeast can escape. Yet, aged yeast cells spawn off youthful daughter cells without any of the telltale protein clumps. Now, researchers at the Stowers Institute for Medical Research may have found an explanation for the observed asymmetrical distribution of damaged proteins between mothers and their youthful daughters.

Reporting in the November 23, 2011, issue of Cell the research team, led by Stowers investigator Rong Li, Ph.D., proposes that the limited mobility of clumps of damaged proteins and yeast cells’ geometry—the narrowness of the connection (bud neck) between the mother and the daughter before their separation, in particular—are sufficient to ensure that protein aggregates accumulated during the normal aging process are retained in the mother cell during cell division.


Cell (Nov. 23, 2011)
Image: Courtesy of Chuankai Zhou, Stowers Institute for Medical Research
The movements of protein aggregates found in old yeast cells follow a "random walk" pattern.

“Harmful protein aggregates had recently been thought to be sent back into the mother cell via a directed transport system,” says Li. “Our model suggests that no active shuttle mechanism may be necessary to help with the asymmetric segregation of protein aggregates during yeast cell divisions.”

In the budding yeast Saccharomyces cerevisae—an important model organisms used in aging research—lifespan can be defined by the number of daughter cells a mother has produced, as opposed to by calendar time, a process known as replicative aging. Daughter cells reset their clock and start counting the number of cell division they have undergone from scratch.

The transition from youth to old age is accompanied by metabolic changes and the accumulation of damage as a result of wear and tear. A central question in aging research is the nature of the damage that contributes to aging and how old mother cells avoid passing on these aging determinants to their daughters.

One factor that is known to correlate with replicative age is the buildup of aggregates formed by damaged proteins. “These proteins are preferentially retained by the mother during bud formation and cell division,” explains Li. “A better understanding of replicative aging of a cell population based on asymmetric cell divisions may provide insights into how higher organisms maintain a population of “youthful” stem cells with high proliferative potential during aging.“

To learn more about the movement and fate of damaged proteins in dividing yeast cells, graduate student and first author Chuankai Zhou with help from Amr Eldakak, Ph.D, a postdoctoral research associate in the Li laboratory, added a green fluorescent tag to Hsp104p, a protein known to modify and dissolve protein aggregates by unfolding and refolding proteins. Zhou then used live-cell imaging to record the movements of thousands of protein aggregates induced by heat in three dimensions.

“Most movements were confined within the bud or the mother but we did see a few movements from bud to mother and vice versa,” says Zhou. “Overall though, we couldn’t detect any directionality in the movements of the aggregates.” In order to rigorously characterize the movement of the protein aggregates, Zhou collaborated with Stowers Research advisors Brian Slaughter, Ph.D., and Jay Unruh, Ph.D., and used particle tracking and computational analysis to show that the aggregate movement is best described as ‘random walk’.

Time-lapse movies also revealed that, over time, heat shock-induced aggregates cleared from all buds and their numbers plummeted in mother cells. When Zhou introduced a mutation into Hsp104p that does not affect Hsp104p’s ability to bind to protein aggregates but disrupts its refolding activity, aggregates no longer cleared from neither mother nor daughter cell. “It told us that heat-induced aggregates dissolved with the help of Hsp104p,” explains Zhou.

Zhou then turned his attention to naturally occurring protein aggregates, which are the result of oxidative damage in cells of older replicative age. He found that these protein clumps followed the same random walk pattern but didn’t dissolve over time. However, these aggregates appeared to move within the confines of the mother without escaping into the bud.

With the help of Stowers research advisor Boris Rubinstein, the team used 3D numerical simulations as well as a 1D analytical model to show that the limited, random mobility of the aggregates was sufficient to explain their preferential retention in the mother, and that the narrow opening of the bud neck further helps trapping the aggregates within the mother prior to cell division.

The research was supported primarily by a grant from the National Institute of Health.

About the Stowers Institute for Medical Research

The Stowers Institute for Medical Research is a non-profit, basic biomedical research organization dedicated to improving human health by studying the fundamental processes of life. Jim Stowers, founder of American Century Investments, and his wife Virginia opened the Institute in 2000. Since then, the Institute has spent over 800 million dollars in pursuit of its mission.

Currently the Institute is home to over 500 researchers and support personnel; over 20 independent research programs; and more than a dozen technology development and core facilities. Learn more about the Institute at www.stowers.org.

Gina Kirchweger | Newswise Science News
Further information:
http://www.stowers.org

More articles from Life Sciences:

nachricht Shrews shrink in winter and regrow in spring
24.10.2017 | Max-Planck-Institut für Ornithologie

nachricht 'Y' a protein unicorn might matter in glaucoma
23.10.2017 | Georgia Institute of Technology

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Salmonella as a tumour medication

HZI researchers developed a bacterial strain that can be used in cancer therapy

Salmonellae are dangerous pathogens that enter the body via contaminated food and can cause severe infections. But these bacteria are also known to target...

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

3rd Symposium on Driving Simulation

23.10.2017 | Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

 
Latest News

Shrews shrink in winter and regrow in spring

24.10.2017 | Life Sciences

Microfluidics probe 'cholesterol' of the oil industry

23.10.2017 | Life Sciences

Gamma rays will reach beyond the limits of light

23.10.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>