Forum for Science, Industry and Business

New Insights into Cellular Death and the Aging Process

Protein researchers at the Ruhr University on the team from Junior Professors Dr. Clemens Steegborn and Dr. Dirk Wolters have clarified a complex safety mechanism that drives damaged cells to cell death when they can no longer be rescued. They identified on the one hand the part of Protein p66Shc that is responsible for a cell's suicide and they additionally ascertained the precise mechanism of its regulation.

In order for the self-destruction to be initiated, several protein components must work together as a complex. The complex can apparently be decomposed by the cell's repair mechanisms for precisely as long as the cell damages are reparable. Only when the cell is defective beyond repair does it perish. The researchers report on their work in the current issue of Proceedings of the National Academy of Sciences (PNAS).

Programmed Cell Death Provides Protection from Malfunctions and Diseases

The function and fate of a cell and subsequently also the functionality and lifespan of a complete organism are controlled by a complex network of signal proteins. Damages and malfunctions in this network are the cause of the aging process and a broad range of diseases which often occur more frequently with increasing age. One important protective mechanism against such malfunctions is programmed cell death, also known as apoptosis, by means of which heavily damaged cells decompose by themselves when their correct function is no longer assured.

Contributes to Arteriosclerosis and Age-Related Diabetes

Signal protein p66Shc functions as a molecular guardian and activates apoptosis as a solution to heavy cellular stress such as UV damage or toxic chemicals. "Mice in which the gene for p66Shc, which is closely related to the human equivalent, has been removed do in fact live some 30 % longer than normal mice, but the suspicion is that this gain in lifespan is achieved at the expense of correct function; i.e., that the organism is more susceptible to malfunctions due to cell damage", explains Dr. Steegborn. P66Shc plays a role in numerous aging-related diseases, for example arteriosclerosis or age-related diabetes. This makes the protein an interesting object for research, both in terms of the aging process and as a possible source of new medications. Despite its significance, the molecular mechanisms of p66Shc-induced apoptosis had nevertheless previously been insufficiently described.

Suicide Protein Under Strict Control

In their study, the Bochum-based researchers were initially able to identify the part of the p66Shc protein responsible for the apoptotic activity. It is a protein domain that produces hydrogen peroxide, a cell toxin, when amended with copper. "It is obvious that this toxic function of p66Shc must be subject to strict control", according to Dr. Steegborn. This is why for example the protein, after its activation, is transported into the mitochondria, the cell's power station, where it then initiates apoptosis.

Protective Mechanisms Can Break Down Stress and the Apoptosis Complex

The protein researchers were also able to explain an additional regulation mechanism: Activated by cellular stress, four p66Shc molecules form a stabile complex via Cystein-Cystein interactions . Only this complex can introduce the controlled cell death by causing the mitochondria to burst. The p66Shc activity can be arrested by the Glutathione and Thioredoxin cellular protective systems, which are capable of breaking down stress damages, substances that cause stress and the activated p66Shc complex. "p66Shc acts in this capacity as a stress sensor", explains Dr. Steegborn. "The cell's suicide program is apparently only started when these protective systems can no longer handle the cellular stress, and are subsequently also no long capable of deactivating p66Shc that has already been activated." These findings on the functionality and molecular regulation of p66Shc improve the understanding of the aging and disease process, and might in the future enable new approaches for intervention with effective agents.

Heading

Melanie Gertz; Frank Fischer; Dirk Wolters; Clemens Steegborn: Activation of the lifespan regulator p66Shc through reversible disulfide bond formation. In: PNAS, April 15, 2008 vol. 105, no. 15, 5705-5709

Additional Information

Junior Professor Dr. Clemens Steegborn, Institut für Physiologische Chemie, Medizinische Fakultät der Ruhr-Universität Bochum, 44780 Bochum, Germany Tel. +49-(0)234/32-27041, E-Mail: Clemens.Steegborn@rub.de

Dr. Josef König | idw
Further information:
http://www.ruhr-uni-bochum.de/physiolchem/steegborn/

Im Focus: Light from a roll – hybrid OLED creates innovative and functional luminous surfaces

Up to now, OLEDs have been used exclusively as a novel lighting technology for use in luminaires and lamps. However, flexible organic technology can offer much more: as an active lighting surface, it can be combined with a wide variety of materials, not just to modify but to revolutionize the functionality and design of countless existing products. To exemplify this, the Fraunhofer FEP together with the company EMDE development of light GmbH will be presenting hybrid flexible OLEDs integrated into textile designs within the EU-funded project PI-SCALE for the first time at LOPEC (March 19-21, 2019 in Munich, Germany) as examples of some of the many possible applications.

The Fraunhofer FEP, a provider of research and development services in the field of organic electronics, has long been involved in the development of...

Im Focus: Regensburg physicists watch electron transfer in a single molecule

For the first time, an international team of scientists based in Regensburg, Germany, has recorded the orbitals of single molecules in different charge states in a novel type of microscopy. The research findings are published under the title “Mapping orbital changes upon electron transfer with tunneling microscopy on insulators” in the prestigious journal “Nature”.

The building blocks of matter surrounding us are atoms and molecules. The properties of that matter, however, are often not set by these building blocks...

Im Focus: University of Konstanz gains new insights into the recent development of the human immune system

Scientists at the University of Konstanz identify fierce competition between the human immune system and bacterial pathogens

Cell biologists from the University of Konstanz shed light on a recent evolutionary process in the human immune system and publish their findings in the...

Im Focus: Transformation through Light

Laser physicists have taken snapshots of carbon molecules C₆₀ showing how they transform in intense infrared light

When carbon molecules C₆₀ are exposed to an intense infrared light, they change their ball-like structure to a more elongated version. This has now been...

Im Focus: Famous “sandpile model” shown to move like a traveling sand dune

Researchers at IST Austria find new property of important physical model. Results published in PNAS

The so-called Abelian sandpile model has been studied by scientists for more than 30 years to better understand a physical phenomenon called self-organized...