Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Cell death pathway linked to mitochondrial fusion

25.01.2011
New research led by UC Davis scientists provides insight into why some body organs are more susceptible to cell death than others and could eventually lead to advances in treating or preventing heart attack or stroke.

In a paper published Jan. 21 in the journal Molecular Cell, the UC Davis team and their collaborators at the National Institutes of Health and Johns Hopkins University report that Bax, a factor known to promote cell death, is also involved in regulating the behavior of mitochondria, the structures that provide energy inside living cells.

Mitochondria constantly split and fuse. The proteins that control the splitting of mitochondria also promote a process called apoptosis, or programmed cell death. In contrast, the proteins that control mitochondrial fusion help protect against cell death. Cell death can happen when cells are starved of oxygen, for example during a heart attack or stroke.

Yeast have a single protein that controls outer membrane fusion, but both human and mouse cells have two proteins, called MFN1 and MFN2, which control outer membrane fusion. Using mitochondria from cells derived from genetically modified "knockout" mice, Suzanne Hoppins, a postdoctoral researcher at UC Davis, and Jodi Nunnari, a professor of molecular cell biology, studied how these two proteins work together and the role specific genes play in that process.

The research team discovered that these proteins combine with themselves or each other to form a tether between two mitochondria, leading to fusion. All three combinations -- MFN1/MFN1, MFN1/MFN2 and MFN2/MFN2 -- can promote membrane fusion, but the combination of MFN1/MFN2 is by far the most efficient, Hoppins said.

Hoppins also found that a soluble form of Bax, a protein that triggers apoptosis, can also stimulate mitochondria to fuse. It acts only through the MFN2/MFN2 combination, she found.

The form of Bax that promotes mitochondrial fusion is different from the type that leads to cell death, Nunnari said. Bax leads to cell death when it inserts itself in the mitochondrial membrane. In its soluble, free-floating form, it causes mitochondria to fuse instead.

MFN1 and MFN2 are found in different amounts in different body organs. MFN2 is more abundant in the brain and heart -- tissues where cell death can have disastrous consequences.

The paper shows how MFN2 could act to protect the brain or heart from cell death, by using Bax in a different form, Nunnari said.

"This shows that the fusion machine is both positively and negatively regulated in cells and opens doors to finding the regulatory mechanisms and discovering ways to increase or decrease the sensitivity of cells to apoptosis," Hoppins said. That could lead to new drugs that save cells, for heart disease and stroke, or that kill cells, for cancer.

Co-authors of the study are UC Davis graduate student Megan Cleland; UC Davis postdoctoral researchers Frank Edlich and Soojay Banerjee; and Richard Youle, a senior investigator at the National Institute for Neurological Disorders and Stroke; and J. Michael McCaffery, a professor at Johns Hopkins University.

The research was supported by grants from the National Institutes of Health. Hoppins recently received a K99 "Young Investigator" award from the NIH.

Media contact(s):
Jodi Nunnari, Molecular and Cellular Biology, (530) 754-9774, jmnunnari@ucdavis.edu

Andy Fell, UC Davis News Service, (530) 752-4533, ahfell@ucdavis.edu

Andy Fell | EurekAlert!
Further information:
http://www.ucdavis.edu

More articles from Life Sciences:

nachricht What happens in the cell nucleus after fertilization
06.12.2016 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Researchers uncover protein-based “cancer signature”
05.12.2016 | 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: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

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

14.10.2016 | Event News

 
Latest News

Speed data for the brain’s navigation system

06.12.2016 | Health and Medicine

What happens in the cell nucleus after fertilization

06.12.2016 | Life Sciences

IHP presents the fastest silicon-based transistor in the world

05.12.2016 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>