Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Mitochondria control stem cell fate

27.10.2016

What happens in intestinal epithelial cells during a chronic illness? Basic research conducted at the Chair of Nutrition and Immunology at the Technical University of Munich (TUM) addressed this question by generating a new model system. Functioning mitochondria play a decisive role in cellular homeostasis, but what happens when an important player of the anti-stress program in mitochondria is switched off? On the one hand, this leads to the loss of stem cells, but on the other, it sets healing processes in motion.

The human intestinal system covers an area of approximately 300 to 500 square meters due to its many protrusions (villi). This inner intestinal wall full of tiny bumps renews itself completely once every four to five days, a process which is guided by stem cells. Mitochondria are the powerhouse of a cell and provide energy through respiration, and play a crucial part in this process.


HSP60 in mitochondria control stem cell proliferation in the gut epithelium. HSP60 negative crypts show a loss of positive stem cells (brown staining).

Photo: Team Haller/ TUM

When the self-renewal of intestinal epithelial cells is interrupted, for example due to defective mitochondria, chronic inflammation may result under extreme conditions. "We then speak of cell stress," explains Professor Dirk Haller from the Chair of Nutrition and Immunology and Executive Director of the Institute for Food and Health (ZIEL) at the Technical University of Munich (TUM).

If cell stress occurs, then – to put it graphically - helpers so called chaperones are activated to ensure that the proteins involved in the renewal process fold properly in cells in order to maintain homeostasis of the intestinal mucosa. Heat shock protein (HSP) 60 is one of these regulators and is essential to maintain the status quo in mitochondria of intestinal epithelial cells.

Study with deactivated heat shock proteins

In a study just published in Nature Communications by Haller and his team, this protein HSP60 was examined more closely. It is deeply involved in the unfolded protein response (UPR), as scientists call it – it can be understood as a component of the anti-stress program in cells. What happens when precisely this crucial regulator HSP60 is deactivated in the gut? How do mitochondria react in the cells when it is absent?

On one hand, the respiratory capacity and the cellular ATP levels were reduced, both key tasks of the mitochondrion, the powerhouse of the cell. At the same time, Professor Haller and his team observed that all cells without HSP60 presented changes. Stem cells lost their ability to self-regenerate, while surrounding epithelial cells initiated a growth program.

Tissue regeneration due to the induction of a growth environment

"But the reaction to the lack of HSP60 was startling", says Haller — "because although stem cells lost their characteristic properties, the stressed cells in the surrounding intestinal mucus wall activated a growth program leading first to hyperproliferation that finally ended in tissue regeneration." The cells with disrupted mitochondrial functions send out growth factors as a "call for help". Using the stress response program, they ensure that the residing stem cells with intact mitochondria divide abundantly; these new, intact cells then replace the other stressed ones.

The lack of HSP60 therefore led to the establishment of communications from one cell to another, triggering a previously unknown healing mechanism which could be of significance after injuries to or inflammation of the intestine. "This shows what a fundamental role functioning mitochondria have in regulating intestinal tissue renewal and how they might contribute to chronic intestinal diseases", says Haller about the findings. Consequently, when the intestine is in a permanent inflammatory or stressed state, the stem cells are permanently over-stimulated to self-renew and this could facilitate the development of tumors.

Publication:

Emanuel Berger, Eva Rath, Detian Yuan, Nadine Waldschmitt, Sevana Khaloian, Michael Allgäuer, Ori Staszewski, Elena M Lobner, Theresa Schöttl, Pieter Giesbertz, Olivia I Coleman, Marco Prinz, Achim Weber, Markus Gerhard, Martin Klingenspor, Klaus-Peter Janssen, Mathias Heikenwalder, and Dirk Haller: Mitochondrial function controls intestinal epithelial stemness and proliferation, Nature Communications 2016, DOI: 10.1038 ncomms13171.

Contact:

Prof. Dr. Dirk Haller
Technical University of Munich
Chair of Nutrition and Immunology
ZIEL - Institute for Food & Health (Director)
Gregor-Mendel-Str. 2
85354 Freising

www.nutrition-immonology.de

dirk.haller@tum.de

Weitere Informationen:

https://www.tum.de/die-tum/aktuelles/pressemitteilungen/kurz/article/33467/

Dr. Ulrich Marsch | Technische Universität München

More articles from Life Sciences:

nachricht Climate Impact Research in Hannover: Small Plants against Large Waves
17.08.2018 | Leibniz Universität Hannover

nachricht First transcription atlas of all wheat genes expands prospects for research and cultivation
17.08.2018 | Leibniz-Institut für Pflanzengenetik und Kulturpflanzenforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Color effects from transparent 3D-printed nanostructures

New design tool automatically creates nanostructure 3D-print templates for user-given colors
Scientists present work at prestigious SIGGRAPH conference

Most of the objects we see are colored by pigments, but using pigments has disadvantages: such colors can fade, industrial pigments are often toxic, and...

Im Focus: Unraveling the nature of 'whistlers' from space in the lab

A new study sheds light on how ultralow frequency radio waves and plasmas interact

Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.

When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

Im Focus: The “TRiC” to folding actin

Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.

Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

LaserForum 2018 deals with 3D production of components

17.08.2018 | Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

 
Latest News

Smallest transistor worldwide switches current with a single atom in solid electrolyte

17.08.2018 | Physics and Astronomy

Robots as Tools and Partners in Rehabilitation

17.08.2018 | Information Technology

Climate Impact Research in Hannover: Small Plants against Large Waves

17.08.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>