Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Cellular Power Plants Also Fend Off Viruses


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:

More articles from Life Sciences:

nachricht When fat cells change their colour
28.10.2016 | Albert-Ludwigs-Universität Freiburg im Breisgau

nachricht Aquaculture: Clear Water Thanks to Cork
28.10.2016 | Technologie Lizenz-Büro (TLB) der Baden-Württembergischen Hochschulen GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Novel light sources made of 2D materials

Physicists from the University of Würzburg have designed a light source that emits photon pairs. Two-photon sources are particularly well suited for tap-proof data encryption. The experiment's key ingredients: a semiconductor crystal and some sticky tape.

So-called monolayers are at the heart of the research activities. These "super materials" (as the prestigious science magazine "Nature" puts it) have been...

Im Focus: Etching Microstructures with Lasers

Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.

This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...

Im Focus: Light-driven atomic rotations excite magnetic waves

Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion

Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Prototype device for measuring graphene-based electromagnetic radiation created

28.10.2016 | Power and Electrical Engineering

Gamma ray camera offers new view on ultra-high energy electrons in plasma

28.10.2016 | Physics and Astronomy

When fat cells change their colour

28.10.2016 | Life Sciences

More VideoLinks >>>