Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Immune Cells Kill Foes by Disrupting Mitochondria Two Ways

19.05.2008
T cells can initiate cellular suicide, also known as apoptosis, by a previously unrecognized pathway that starts with the destruction of a key enzyme in mitochondria, the power plant of the cell.

When killer T cells of the immune system encounter virus-infected or cancer cells, they unload a lethal mix of toxic proteins that trigger the target cells to self-destruct. A new study shows T cells can initiate cellular suicide, also known as programmed cell death or apoptosis, by a previously unrecognized pathway that starts with the destruction of a key enzyme in mitochondria, the power plant of the cell.

The study, from the lab of Judy Lieberman, a senior investigator at the Immune Disease Institute and Professor of Pediatrics at Harvard Medical School, reveals that T cells use both the novel pathway and the classical apoptotic pathway to interfere with mitochondrial function and induce cell death.

“This work gives us a new understanding of a major T cell defense pathway,” Lieberman says. The results will appear in the May 16 issue of Cell.

The Lieberman lab studies cytotoxic T lymphocytes (CTLs), key cells in the immune defense against viral infection and cancer. When CTLs recognize an infected or transformed target cell, they release the contents of cytolytic granules onto the target cell. These granules contain serine proteases called Granzymes, which induce programmed cell death in the target cells. Two major Granzymes, A and B, account for most of the killing activity in granules.

Granzyme B triggers the classical programmed cell death pathway involving breakdown of the outer mitochondrial membrane, and the release of death-promoting proteins which activate the caspase protease cascade and result in massive DNA damage.

Previous work from the Liebeman lab showed that Granzyme A initiates cell death by a different biochemical pathway. That pathway involves the mitochondria, but does not result in mitochondrial membrane breakdown or caspase activation, and triggers a different type of DNA damage. The current study was aimed at understanding how Granzyme A kills cells.

To identify Granzyme A target proteins in mitochondria, Lieberman and colleagues used proteomics to look at the fate of a large number of mitochondrial proteins after Granzyme A exposure. One protein, NDUFS3, a subunit of the large multi-protein Complex I assembly that participates in energy generation for the cell, disappeared.

Further work established that when Granzyme A was released into a cell, it could enter the mitochondria where it degraded NDUFS3. Further, the investigators showed that loss of NDUFS3 caused mitochondria to produce damaging reactive oxygen, known to be essential for Granzyme A’s deadly effects on cells. Destruction of NDUFS3 was sufficient to initiate the toxic effects of Granzyme A on human cells, they showed.

The new demonstrate that while both Granzymes target mitochondria, they do so in very different ways. Lieberman says she is not surprised that immune cells have multiple means of inducing mitochondrial-dependent cell death. “Many viruses and cancers have found ways to be resistant to the caspase-dependent apoptosis pathway triggered by Granzyme B, so it makes sense that immune cells would have a second, parallel pathway to cause cell death,” she said.

Written by Pat McCaffrey

The lead author on the paper is Denis Martinvalet, a postdoctoral fellow in the Lieberman lab. Other authors include Derek M Dykxhoorn, and Roger Ferrini of the Immune Disease Institute.

David Cameron | Harvard Medical School
Further information:
http://www.hms.harvard.edu

Further reports about: Granzyme Lieberman NDUFS3 Protein immune initiate mitochondria mitochondrial

More articles from Life Sciences:

nachricht Show me your leaves - Health check for urban trees
12.12.2017 | Gesellschaft für Ökologie e.V.

nachricht Liver Cancer: Lipid Synthesis Promotes Tumor Formation
12.12.2017 | Universität Basel

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Long-lived storage of a photonic qubit for worldwide teleportation

MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.

Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...

Im Focus: Electromagnetic water cloak eliminates drag and wake

Detailed calculations show water cloaks are feasible with today's technology

Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...

Im Focus: Scientists channel graphene to understand filtration and ion transport into cells

Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.

To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...

Im Focus: Towards data storage at the single molecule level

The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.

Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...

Im Focus: Successful Mechanical Testing of Nanowires

With innovative experiments, researchers at the Helmholtz-Zentrums Geesthacht and the Technical University Hamburg unravel why tiny metallic structures are extremely strong

Light-weight and simultaneously strong – porous metallic nanomaterials promise interesting applications as, for instance, for future aeroplanes with enhanced...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

AKL’18: The opportunities and challenges of digitalization in the laser industry

07.12.2017 | Event News

 
Latest News

Long-lived storage of a photonic qubit for worldwide teleportation

12.12.2017 | Physics and Astronomy

Multi-year submarine-canyon study challenges textbook theories about turbidity currents

12.12.2017 | Earth Sciences

Electromagnetic water cloak eliminates drag and wake

12.12.2017 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>