Featured Research

from universities, journals, and other organizations

Body's own recycling system: Researchers discover 'molecular emergency brake' in charge of regulating self-digestion

Date:
October 12, 2012
Source:
Helmholtz Centre for Infection Research
Summary:
Times of distress literally eat away at the core of starving cells: They start to digest their own parts and recycle them for metabolic purposes. Researchers have discovered that a "molecular brake" is in charge of regulating autophagy to keep it from getting out of control.

Using a microscope, the researchers are able to zoom in on the cells: If autophagy proceeds undisturbed, they are able to observe little digestive bubbles, shown in red, inside of which material is being degraded (left). If the final step is blocked, autophagosomes accumulate inside the cell, shown here in green (right). The dark circular area at the center is the nucleus.
Credit: Ralf Höcker/HZI

Times of distress literally eat away at the core of starving cells: They start to digest their own parts and recycle them for metabolic purposes. This process -- called autophagy -- also plays a role in immune defense. In that context, however, the digestive machinery is switched on for an entirely different purpose: the elimination of pathogens that have invaded the body. Now, Prof. Ingo Schmitz at the Helmholtz Centre for Infection Research (HZI) in Braunschweig, Germany, together with a team of researchers, has discovered that a "molecular brake" is in charge of regulating autophagy to keep it from getting out of control.

Related Articles


They published their findings in the scientific journal Cell Death & Differentiation.

Almost everything that happens inside a cell, including autophagy, is tightly regulated on a biochemical level. Like that, the cell makes sure that processes only take place when they are needed and that they are shut off when the need has expired. "Inside the cell, there exists a network of molecules. Between them, information is constantly being exchanged," says Schmitz, head of the research group "Systems-oriented Immunology and Inflammation Research" at HZI, who also holds a chair at the Otto von Guericke University in Magdeburg. "In a way, it looks like a big city subway map." However, only the starting point and the destination of a given "cellular subway line" are relatively easy to study. To explore the different stops along the way, is more difficult. But because other lines intersect and interact with each other at these points, it is very exciting for researchers to decode all molecules involved in these signal transduction processes. It also helps them better understand diseases caused by defects in these information highways.

What exactly happens on a molecular level during the later stages of autophagy was largely unknown -- until now. Schmitz and his team, along with researchers from the Otto von Guericke University Magdeburg, the Heinrich Heine University Düsseldorf, the Tübingen University, and the Temple University School of Medicine in Philadelphia, USA, have decoded one part of the molecular subway map.

Under the microscope, researchers can observe how larger-sized cellular components destined for degradation and recycling are enclosed within a small bubble, the so-called autophagosome. This structure then fuses with yet another little bubble, which digests the autophagosome's contents. "Autophagy is a survival mechanism to ensure that the cell is able to obtain the necessary nutrients during times of starvation," explains Schmitz.

For their studies, the scientists stained certain molecules and autophagosomes inside cells. This allowed them to observe microscopically which molecules are in charge of regulating the formation of the little digestive bubbles. To prompt self-digestion, they either starved the cells or simulated an infection. In the process, they discovered that the cells simultaneously also turned on autophagy-inhibiting molecules -- "like some kind of emergency brake that ensures autophagy doesn't get out of control." Such negative feedback loops are not unusual for cells, they frequently help prevent overshooting reactions.

The researchers managed to identify the components of this feedback loop and found a protein called p38 to play a key role in the process. The scientists were especially surprised to observe p38 proteins on the surface of the autophagosomes. Normally, this protein is localized inside the nucleus where it gets switched on whenever the cell is under stress. On the surfaces of autophagosomes, p38 performs a very different job: It alters another molecule, called Atg5, to get it to block the final step of autophagy, involving formation of the little digestive bubble. Autophagy is inhibited, and, essentially, the cell pulls the "molecular emergency brake."

If it didn't, diseases could potentially result. As such, defective molecules of the Atg family have been implicated in the etiology of the inflammatory bowel disease, Morbus Crohn. "Looking at Atg5-deficient mice, which die of nutrient-deficiency shortly after they are born, we see just how important it is to tightly regulate autophagy," emphasizes Ralf Höcker, one of the study's first authors. As so often, it is important to find the right balance, in this case, between too much and too little self-digestion.


Story Source:

The above story is based on materials provided by Helmholtz Centre for Infection Research. Note: Materials may be edited for content and length.


Journal Reference:

  1. E Keil, R Höcker, M Schuster, F Essmann, N Ueffing, B Hoffman, D A Liebermann, K Pfeffer, K Schulze-Osthoff, I Schmitz. Phosphorylation of Atg5 by the Gadd45β–MEKK4-p38 pathway inhibits autophagy. Cell Death and Differentiation, 2012; DOI: 10.1038/cdd.2012.129

Cite This Page:

Helmholtz Centre for Infection Research. "Body's own recycling system: Researchers discover 'molecular emergency brake' in charge of regulating self-digestion." ScienceDaily. ScienceDaily, 12 October 2012. <www.sciencedaily.com/releases/2012/10/121012112422.htm>.
Helmholtz Centre for Infection Research. (2012, October 12). Body's own recycling system: Researchers discover 'molecular emergency brake' in charge of regulating self-digestion. ScienceDaily. Retrieved December 18, 2014 from www.sciencedaily.com/releases/2012/10/121012112422.htm
Helmholtz Centre for Infection Research. "Body's own recycling system: Researchers discover 'molecular emergency brake' in charge of regulating self-digestion." ScienceDaily. www.sciencedaily.com/releases/2012/10/121012112422.htm (accessed December 18, 2014).

Share This


More From ScienceDaily



More Plants & Animals News

Thursday, December 18, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Navy Unveils Robot Fish

Navy Unveils Robot Fish

Reuters - Light News Video Online (Dec. 18, 2014) — The U.S. Navy unveils an underwater device that mimics the movement of a fish. Tara Cleary reports. Video provided by Reuters
Powered by NewsLook.com
Kids Die While Under Protective Services

Kids Die While Under Protective Services

AP (Dec. 18, 2014) — As part of a six-month investigation of child maltreatment deaths, the AP found that hundreds of deaths from horrific abuse and neglect could have been prevented. AP's Haven Daley reports. (Dec. 18) Video provided by AP
Powered by NewsLook.com
When You Lose Weight, This Is Where The Fat Goes

When You Lose Weight, This Is Where The Fat Goes

Newsy (Dec. 17, 2014) — Can fat disappear into thin air? New research finds that during weight loss, over 80 percent of a person's fat molecules escape through the lungs. Video provided by Newsy
Powered by NewsLook.com
The Hottest Food Trends for 2015

The Hottest Food Trends for 2015

Buzz60 (Dec. 17, 2014) — Urbanspoon predicts whicg food trends will dominate the culinary scene in 2015. Mara Montalbano (@maramontalbano) has the story. Video provided by Buzz60
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

Strange & Offbeat Stories

 

Plants & Animals

Earth & Climate

Fossils & Ruins

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins