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.
What happens in intestinal epithelial cells during a chronic illness? Basic research 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.
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 senior author. 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.
In a study just published in Nature Communications, 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, the 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.
"But the reaction to the lack of HSP60 was startling", says the author -- "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 the author 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.
https://www.tum.de/en/about-tum/news/press-releases/short/article/33467/
http://www.nature.com/articles/ncomms13171
Mitochondria control stem cell fate
- 2,024 views
- Added
Edited
Latest News
Complete vascularization of…
By newseditor
Posted 28 Mar
Immune cells identified as…
By newseditor
Posted 28 Mar
TB blood test which could d…
By newseditor
Posted 27 Mar
Propionate supplementation…
By newseditor
Posted 27 Mar
Role of human Kallistatin i…
By newseditor
Posted 26 Mar
Other Top Stories
Exposure to farm microbes protect against childhood asthma
Read more
Artificial intelligence to predict customized anti-cancer drug effi…
Read more
Antibody-mediated weight reduction in obese humans
Read more
Neuronal Autophagy Regulates Presynaptic Neurotransmission
Read more
Brain gene that controls food cravings, desire to exercise identified!
Read more
Protocols
Spatial proteomics in neuro…
By newseditor
Posted 28 Mar
All-optical presynaptic pla…
By newseditor
Posted 23 Mar
Epigenomic tomography for p…
By newseditor
Posted 20 Mar
A mouse DRG genetic toolkit…
By newseditor
Posted 17 Mar
An optogenetic method for t…
By newseditor
Posted 13 Mar
Publications
A microfluidic platform int…
By newseditor
Posted 28 Mar
Salmonella manipulates macr…
By newseditor
Posted 28 Mar
BHLHE40/41 regulate microgl…
By newseditor
Posted 28 Mar
Balancing neuronal activity…
By newseditor
Posted 28 Mar
OSBP-mediated PI(4)P-choles…
By newseditor
Posted 28 Mar
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar