Atossa - The protein queen commanding cell invasion
Scientists discover novel master regulator that boosts an immune cell's
energy for tissue invasion
Date:
March 23, 2022
Source:
Institute of Science and Technology Austria
Summary:
Immune cells are our body's police force, but how can they reach
the crime scene fast? Researchers have now discovered a new protein
that boosts energy production inside immune cells and thus increases
their power to invade. Apart from improving immune responses, the
results could revolutionize our understanding of energy regulation
in cells throughout the human body.
FULL STORY ==========================================================================
For life to survive, it needs to respond to challenges, particularly by adapting the activity of its immune system. As we have seen with Covid,
outside infectious agents are constantly trying to gain a foothold
within the body. But how can immune cells move into new tissues to find
and destroy such infections? By investigating this crucial process,
Professor Daria Siekhaus and Dr. Shamsi Emtenani from her group at ISTA
ended up answering an even bigger question: What governs the energy
needed for cell invasion?
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They discovered a two-fold program that boosts energy production
inside immune cells, thereby supplying the power needed for their
invasion into tissues. This novel pathway is governed by a previously
unstudied protein which they named Atossa after a Persian queen. While
the experiments were done in the fruit fly, the researchers' results show
that similar proteins in mammals exhibit the same function. "There is a plethora of potential for how this work can lead to new perspectives of
human physiology, because boosting energy production is essential in so
many cells throughout the human body," says lead author Emtenani. Their collaborative work with the University of Albany, University of Toronto,
the CeMM Research Center and the Vienna BioCenter is now published in
the journal of the European Molecular Biology Organization (EMBO).
Atossa, ruling to boost energy For cells, pushing surroundings out of
the way and moving into tissues is energetically costly. The immune
system ramps up energy by using mitochondria, the cell's internal
powerhouse. Mitochondria turn various constituents like sugar into ATP,
the cellular currency of energy. The researchers have now found that one protein, Atossa, orchestrates a cascade that regulates and improves the capacity of mitochondria to produce energy.
"Atossa acts as both an accelerator pedal and a gear shift," explains
Siekhaus.
"First, the protein activates two metabolic enzymes that help send
more fuel into the mitochondrial factory, and second, it shifts the mitochondria into a higher gear." This gear shift is caused by Atossa's increasing the levels of the protein Porthos, an RNA helicase named
after one of the three musketeers known for their faithfulness in
serving their queen. Then, Porthos aids the assembly of the machinery
that enables protein production through translation, including many that
raise mitochondrial activity and thus energy production.
Pioneering fly work relevant for human health By live imaging of fruit
fly embryos, the researchers were able to detect a clear reduction in cell migration in the absence of Atossa. Also, Atossa's function is only needed
in pioneer cells. Much like an expedition through a thicket, the first
cells do the hard work of clearing a path with the machete and thus need
more energy. With the support of collaborator Dr. Thomas Ko"cher from the Vienna BioCenter, the ISTA scientists compared the energy levels with and without the Atossa gene and confirmed that Atossa indeed enhances them.
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A master regulator like Atossa is, however, not only present in fruit
flies.
The responsible protein code in flies is 44 percent identical to
comparable ones in humans. Indeed, the researchers demonstrated that
the mammalian genes can substitute for the function of the fruit fly
protein. "We are very intrigued by the possibilities this opens up. Atossa could be of key importance for upregulating energy production. In
immune cells, this is relevant for example in antibody production and
the specification of white blood cells.
Atossa-like proteins are also found in brain cells. Here, defects have
been shown to underlie neurodegenerative diseases," says Siekhaus,
pointing to future research avenues.
The legacy of an Iranian woman "Fly work is the premiere place to nail
down complicated genetic mechanisms and identify new things. It takes
enormous courage and great cleverness to analyze something completely unexplored. To me, Shamsi's work, proving every step of the cascade, is
an example of the best science you can do in this field," Siekhaus lauds
the Iranian, who has joined her laboratory in 2015. Shamsi Emtenani adds:
"I looked at this specific gene out of curiosity. The exciting thing is:
If you are the first one that discovers a gene's function in the fruit
fly field, you get the chance to name its protein." Formerly indexed as CG9005, Emtenani named the protein Atossa. Since the pioneer cells move
in a line, one by one, almost like a stream of water, she chose the name
of a Persian queen from the Achaemenid Empire. "Atossa literally means 'trickling' and it connects to my background. It seemed fitting as well
for a queen who commands three proteins -- one of them a musketeer -
- responsible for making cells invade new territories." Video of cell invasion:
https://youtu.be/cYZXN2kbL2w Video explaining function of the
protein Atossa:
https://youtu.be/6AOtWFvpdnk
========================================================================== Story Source: Materials provided by Institute_of_Science_and_Technology_Austria. Note: Content may be edited
for style and length.
========================================================================== Journal Reference:
1. Shamsi Emtenani, Elliot T Martin, Attila Gyoergy, Julia Bicher,
Jakob‐Wendelin Genger, Thomas Ko"cher, Maria Akhmanova,
Mariana Guarda, Marko Roblek, Andreas Bergthaler, Thomas
R Hurd, Prashanth Rangan, Daria E Siekhaus. Macrophage
mitochondrial bioenergetics and tissue invasion are boosted by an
Atossa‐Porthos axis in Drosophila. The EMBO Journal, 2022;
DOI: 10.15252/embj.2021109049 ==========================================================================
Link to news story:
https://www.sciencedaily.com/releases/2022/03/220323125058.htm
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