Nav: Home

When low batteries are a good thing

June 22, 2018

Every day the human gut works on a fine-tuned balance that ensures the retention of essential nutrients while it prevents the entrance of potential armful microbes. Contributing to this surveillance system is a specialised group of immune cells that are held back due to unknown reasons although they have many characteristics of activated cells. Now, a new study led by Marc Veldhoen, group leader at Instituto de Medicina Molecular João Lobo Antunes (iMM; Portugal) shows how these cells are kept under control. The work published now in Science Immunology, reveals that the "batteries" of these cells have a different composition that reduces their capacity of producing energy, keeping them in a controlled activated mode. This knowledge can give rise to new diagnostics and treatments for conditions affecting the digestive track such as gut inflammations or infections.

The outer layer of our bodies, the skin and intestine, contains a special population of white blood cells, called intraepithelial lymphocytes. It is largely unknown how the activity of these cells is controlled, not fully activated nor at rest. Using imaging and biochemical experiments, the research group led by Marc Veldhoen has now shown this is, at least in part, due to differences in the cells' "batteries" - the mitochondria. These energy-producing structures are present inside our cells regulate the cell's power. "We hypothesised that these gut-resident white blood cells may use energy in a different way. It was surprising to see that the detection of mitochondria gave a very different picture than seen in other white blood cells, forming the basis of a new hypothesis that the mitochondria themselves are different in these cells", explains Marc Veldhoen.

Using high magnification electron microscopy, the researchers observed that the mitochondria were present in abundance but seem to be different upon staining for light microscopy. Next, they studied the functionality of these batteries. "When we analysed in detail these structures, we found changes in the lipids that form a layer separating the mitochondria from the rest of the cell", says S?pela Konjar, joint first author of the study, adding that "these changes make the "batteries" work differently, as if they are in a "low energy mode".

When the lipid landscape was purposely altered, the researchers confirmed a change in the activation potential of the cells. "Our results showed that lipids in the mitochondria of these cells could alter their metabolic state and change their activity. When the mitochondrial lipids could not be arranged similar to those found in other white blood cells, the cells could not be properly activated when needed", explains Marc Veldhoen. The researcher further explains: "This knowledge allows us to investigate how we can inhibit these cells when they are too active and cause damage, such as in gut inflammations, or how we can activate them more in cases of gut infections. Furthermore, the detection of mitochondria could be a diagnostic marker for the activation state of intestinal white blood cells".
-end-
This work was performed at the iMM (Portugal) and at the Babraham Institute (UK) with collaborations at Chicago University (USA). It was funded by the European Research Council, the Biotechnology and Biological Sciences Research Council, Horizon 2020 "EXCELLtoINNOV", National Institutes of Health, FEDER through POR Lisboa 2020-Programa Operacional Regional de Lisboa, PORTUGAL 2020, and Fundacao para a Ciencia e a Tecnologia.

*Konjar, S., Frising, U.C., Ferreira, C., Hinterleitner, R., Mayassi, T., Zhang, Q., Blankenhaus, B., Haberman, N., Loo, Y., Guedes, J., Baptista, M., Innocentin, S., Stange, J., Strathdee, D., Jabri, B., Veldhoen, M. (2018) Mitochondria maintain controlled activation state of epithelial-resident T lymphocytes. Sci. Immunol. 3, eaan2543. doi - 10.1126/sciimmunol.aan2543.

Instituto de Medicina Molecular

Related Mitochondria Articles:

Mitochondria-targeted antioxidant SkQ1 helps to treat diabetic wounds
Members of the Faculty of Biology and A.N. Belozersky Institute of Physico-Chemical Biology, a unit of the Lomonosov Moscow State University, have tested on a mouse model a mitochondria-targeted antioxidant, helping to treat diabetic wounds.
Mitochondria targeting anti-tumor compound
Researchers from Kumamoto University in Japan have found that the compound folic acid-conjugated methyl-BETA-cyclodextrin (FA-M-BETA-CyD) has significant antitumor effects on folate receptor-ALPHA-expressing (FR-ALPHA (+)) cancer cells.
Closing the gate to mitochondria
A team of researchers develops a new method that enables the identification of proteins imported into mitochondria.
Elucidated connection between renal failure and 'bad' mitochondria described
Biologists from the A.N. Belozersky Institute of Physico-Chemical Biology, a unit of the Lomonosov Moscow State University suggested the approach to prevent kidney injury after ischemia.
How exercise -- interval training in particular -- helps your mitochondria stave off old age
Researchers have long suspected that the benefits of exercise extend down to the cellular level, but know relatively little about which exercises help cells rebuild key organelles that deteriorate with aging.
Cell disposal faults could contribute to Parkinson's, study finds
A fault with the natural waste disposal system that helps to keep our brain cell 'batteries' healthy may contribute to neurodegenerative disease, a new study has found.
Sex cells evolved to pass on quality mitochondria
Mammals immortalize their genes through eggs and sperm to ensure future generations inherit good quality mitochondria to power the body's cells, according to new UCL research.
Newly identified pathway in mitochondria fuels tumor progression across cancer types
Scientists at The Wistar Institute have identified a novel protein pathway across several types of cancer that controls how tumor cells acquire the energy necessary for movement, invasion and metastasis.
Collapse of mitochondria-associated membrane in ALS
Mitochondria-associated membrane (MAM) is a contacting site of endoplasmic reticulum and mitochondria, and plays a key role in cellular homeostasis.
New research on the muscles of elite athletes: When quality is better than quantity
A Danish-Swedish research team working on a project led by University of Southern Denmark has discovered that muscle endurance is not only determined by the number of mitochondria, but also their structure.

Related Mitochondria Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Changing The World
What does it take to change the world for the better? This hour, TED speakers explore ideas on activism—what motivates it, why it matters, and how each of us can make a difference. Guests include civil rights activist Ruby Sales, labor leader and civil rights activist Dolores Huerta, author Jeremy Heimans, "craftivist" Sarah Corbett, and designer and futurist Angela Oguntala.
Now Playing: Science for the People

#521 The Curious Life of Krill
Krill may be one of the most abundant forms of life on our planet... but it turns out we don't know that much about them. For a create that underpins a massive ocean ecosystem and lives in our oceans in massive numbers, they're surprisingly difficult to study. We sit down and shine some light on these underappreciated crustaceans with Stephen Nicol, Adjunct Professor at the University of Tasmania, Scientific Advisor to the Association of Responsible Krill Harvesting Companies, and author of the book "The Curious Life of Krill: A Conservation Story from the Bottom of the World".