Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Cellular Power Plants Also Fend Off Viruses

26.08.2005


Three confocal microscopic images of a cell stained with an antibody that detects the protein MAVS (left), Mito-Tracker (center), and an overlay of the green and red images (right) that indicates the mitochondrial localization of MAVS. Images courtesy of Zhijian ’James’ Chen, HHMI at UT Southwestern Medical Center


Three confocal microscopic images of a cell stained with an antibody that detects the protein MAVS (left), Mito-Tracker (center), and an overlay of the green and red images (right) that indicates the mitochondrial localization of MAVS.

Researchers have discovered a surprise lurking inside mitochondria, the power plants that are present in every cell. It turns out that these powerhouses also contain a protein that triggers the immune system to attack viral invaders.

According to the researchers, the new role makes perfect biological and evolutionary sense because it fits well with another function of mitochondria as executioners of a biochemical cascade that causes programmed cell death, or apoptosis.



“This is the first protein known to be involved in the immune response that is found in mitochondria,” said Zhijian `James’ Chen, a Howard Hughes Medical Institute investigator at the University of Texas Southwestern Medical Center. Chen and his colleagues reported the discovery on August 25, 2005, in an immediate early publication of the journal Cell.

In their studies, Chen and his colleagues were seeking a regulatory molecule that would provide a missing link in the activation of two important triggers of the innate immune system — NF-kB and IRF3. Somehow, these molecules are activated in response to a receptor molecule, called RIG-I, which detects viral genetic material. RIG-I binds to the RNA of viruses such as the influenza virus, hepatitis C virus, West Nile virus and SARS virus.

The researchers knew the molecule they were seeking was present in a biochemical pathway somewhere between RIG-I and other “downstream” regulatory molecules. They initiated a search for this missing molecule by searching for proteins in the cell that contain a characteristic molecular domain, called a CARD domain, which mediates interactions between different regulatory proteins. Their search yielded a protein, which they called MAVS for mitochondrial antiviral signaling.

Their experiments revealed that MAVS activated NF-kB and IRF3 in cell cultures. They also found that in order for MAVS to function, it requires both the CARD domain and another domain that anchors it to the mitochondrial membrane. Studies using fluorescent tracers revealed that MAVS was present in the mitochondria of cells. And when the researchers altered the MAVS molecule in such a way that it prevented MAVS from attaching to mitochondria, the molecule did not function properly.

The researchers demonstrated the importance of MAVS in immune responses by showing that cells without MAVS were vulnerable to viral infection; while those with excess MAVS were resistant to such infections.

Chen speculated that the mitochondria might have evolved into immune sentinels because of their location near internal cell membranes where viral replication takes place. “By having MAVS in the mitochondrial membrane, it provides a strategic position for cells to sense the presence of viruses, especially viral replication,” said Chen.

“In addition, MAVS is unique in that it has both a mitochondrial targeting sequence, as well as a CARD domain sequence,” said Chen. “CARD domain proteins are known to be involved in apoptosis, and the mitochondria are also known to be involved in apoptosis. So, while at this point this is still pure speculation, but perhaps combining these two domains in one protein, MAVS, might allow the cells to integrate signals somehow and coordinate apoptotic responses or immune responses, depending on the type of viral infection.” Apoptosis is triggered when a cell is no longer needed during development or is damaged beyond repair. It serves to protect the body from the accumulation of damaged or malfunctioning cells.

Chen said that the newly discovered immunological service rendered to the cell by mitochondria makes good biological and evolutionary sense. “Evolutionarily, it is believed that mitochondria originated from ancient bacteria, which formed a symbiotic relationship with eukaryotic cells,” said Chen. “For symbiosis to evolve, the bacteria and the host must be beneficial to one another. Mitochondria have long been known to serve the major function of producing chemical energy for the cell, as well as to sense damage and trigger apoptosis. Now, I think our discovery reveals another important function of the mitochondria, and that is in immunity,” he said.

Understanding how boosting MAVS function causes cells to resist viral infection could have important clinical implications, said Chen. “Treatments that enhance the activity of MAVS may prove to be useful in boosting immunity against viruses,” he said. “Furthermore, we suspect that MAVS might be a prime target for some viruses that can evade immune surveillance. If those suspicions prove out, then treatments that counteract this evasion could provide therapeutic benefits,” he said. Chen also speculated that subtle variations in the MAVS protein might explain why people may respond differently when infected with the same virus.

Chen and his colleagues are now exploring such questions, as well as teasing out further molecular details of the signaling mechanism by which MAVS triggers the immune system. “Over the long term, we would like to understand the host-viral interactions that function through MAVS, and how MAVS gives the cell immunity to viruses and how viruses try to evade this function of MAVS. We would like to exploit these findings to develop more effective antiviral strategies.”

Jim Keeley | EurekAlert!
Further information:
http://www.hhmi.org

More articles from Life Sciences:

nachricht Link Discovered between Immune System, Brain Structure and Memory
26.04.2017 | Universität Basel

nachricht Researchers develop eco-friendly, 4-in-1 catalyst
25.04.2017 | Brown 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: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

Scientist invents way to trigger artificial photosynthesis to clean air

26.04.2017 | Materials Sciences

Ammonium nitrogen input increases the synthesis of anticarcinogenic compounds in broccoli

26.04.2017 | Agricultural and Forestry Science

SwRI-led team discovers lull in Mars' giant impact history

26.04.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>