Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

‘Reaper’ protein strikes at mitochondria to kill cells

21.10.2010
Our cells live ever on the verge of suicide, requiring the close attention of a team of molecules to prevent the cells from pulling the trigger.

This self-destructive tendency can be a very good thing, as when dangerous precancerous cells are permitted to kill themselves, but it can also go horribly wrong, destroying brain cells that store memories, for instance.

Rockefeller University scientists are parsing this perilous arrangement in ever finer detail in hopes that understanding the basic mechanisms of programmed cell death, or apoptosis, will enable them eventually to manipulate the process to kill the cells we want to kill and protect the ones we don’t.

In experiments published last month in the Journal of Cell Biology, researchers led by postdoctoral associate Cristinel Sandu in Hermann Steller’s Strang Laboratory of Apoptosis and Cancer Biology drilled down on a protein aptly named Reaper, which was first described in a 1994 paper by Steller in Science. Under the right conditions,

Reaper interferes with molecules called inhibitor of apoptosis proteins (IAPs), which prevent the cell from irrevocably initiating its autodestruct sequence. By inhibiting these inhibitors, Reaper essentially takes the brakes off the process of apoptosis, pronouncing a cell’s death sentence. Other molecules called caspases then carry that sentence out.

“Like the grim reaper, Reaper is an announcer of death, but not the executioner,” says Steller, who is also a Howard Hughes Medical Institute investigator. “It’s like the key that starts the engine.”

Reaper and the other Drosophila IAP antagonists Hid and Grim are known to trigger apoptosis in flies, and related proteins serve a similar function in humans and other mammals. But exactly how and where Reaper initiates apoptosis has not been well understood. Sandu and colleagues bred genetically modified strains of flies that expressed variations on the Reaper protein specifically in flies’ eyes. This allowed them to assess the contribution of individual protein motifs to Reaper’s apoptosis inducing powers, and what they found was that a particular helical domain was crucial for the formation of Reaper complexes, and could be modified to be even more powerful than the regular protein. The more deadly Reaper variants were obvious by the damage caused to the flies’ eyes.

In a series of biochemical experiments, the researchers also found that Reaper must travel to the mitochondria, the cell’s energy factories, to effectively deliver its death sentence, and that to get there, it must hitch a ride on the Hid protein, with which it interacts. By tagging Hid and Reaper fluorescently, Sandu could visualize Hid and Reaper acting in a complex and gathering at the membrane of the mitochondria. When Reaper was engineered to go directly to the mitochondrial membrane, it resulted in a molecule that is far superior at triggering cell death than regular Reaper. Further experiments suggested that in a complex with Hid, Reaper is protected from degradation as the cells began to die.

“So now we have Hid and Reaper working very closely together,” Sandu says. “And the localization to the mitochondria is crucial to the initiation of apoptosis.” Drugs that mimic a small part of the function of Reaper are already in clinical trials. The discovery of a way to make Reaper a much better killer, namely by targeting it directly to the mitochondria, provides new avenues to explore for improving cancer therapies. “Adding this element that takes Reaper directly to the mitochondria is not something people would have thought of before this,” Steller says.

Brett Norman | EurekAlert!
Further information:
http://www.rockefeller.edu

More articles from Life Sciences:

nachricht Study shines light on brain cells that coordinate movement
26.06.2017 | University of Washington Health Sciences/UW Medicine

nachricht New insight into a central biological dogma on ion transport
26.06.2017 | Aarhus 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: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Study shines light on brain cells that coordinate movement

26.06.2017 | Life Sciences

Smooth propagation of spin waves using gold

26.06.2017 | Physics and Astronomy

Switchable DNA mini-machines store information

26.06.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>