Boosting the cell's power house

Date:
October 6, 2021
Source:
Institute of Science and Technology Austria
Summary:
Severe fatigue, muscle weakness, even blindness -- mitochondrial
diseases have various symptoms. In fact, the majority of genetic
diseases are caused by defects of the mitochondria. Hence,
understanding these 'power houses' of our cells is crucial for
the developments of new treatments.

Researchers now show the structure of a protein complex essential
for their work.



FULL STORY ==========================================================================
In order to fulfill their many tasks, cells need energy. In the cell's
power plants, known as mitochondria, the energy contained in our food is converted into the molecule ATP. It serves as a kind of fuel that drives
most cellular processes -- from muscle contraction to the assembly of
our DNA. Professor Leonid Sazanov and Irene Vercellino are now the first scientists to precisely show what a protein assembly essential for this
process looks like in mammalian cells.


==========================================================================
Like a fishhook Using cryo-electron microscopy, a technique that allows researchers to look at extremely small samples in their natural state,
first author Irene Vercellino and Prof. Sazanov show the exact structure
of the so-called supercomplex CIII2CIV. This assembly of protein building blocks pumps charged particles, protons, through the mitochondrial
membrane, which is needed to start the energy conversion process in the
cells. It therefore fulfills a similar task as the starter battery of
cars. Up to now, this supercomplex has only been described in plant and
yeast cells where it takes on a very different form, as the researchers
now discovered. In order to understand how exactly energy production
works in animal cells like our own, the scientists now took a close look
at mice and sheep cells and were surprised.

"Nobody could have predicted the way SCAF1 acts," says Sazanov. Previous studies already showed that the molecule SCAF1 plays a role in
assembling the two protein complexes that together form supercomplex
CIII2CIV. Instead of interacting with the two protein complexes on the
surface only, the molecule goes deep inside complex III while being
attached to complex IV. "It is like a hook swallowed by a fish. Once
it's swallowed it can't get out," the structural biologist explains.

Close, but not too close Furthermore, the scientists show that
supercomplex CIII2CIV takes on two different forms -- a locked and an
unlocked or mature one. "In its locked state some parts of complex III
are still missing and the interaction between the two complexes is very intimate," describes Sazanov. Once it is fully assembled, however, the two complexes are connected by SCAF1 without getting in each other's way. "In
order to fulfill its tasks, complex III probably prefers to be free from interference in its movements," the Belarusian-British scientist assumes.

Being assembled into a supercomplex, on the other hand, speeds up their chemical reactions, which has great advantages for the animal. It has
been shown, that mice and zebrafish missing the SCAF1 molecule are significantly smaller, less fit, and less fertile. In their recent
study, Vercellino and Sazanov describe the molecule's role in forming supercomplex CIII2CIV, which optimizes the cellular metabolism. It has
been the final piece of the puzzle: together with their previous studies, Sazanov and his team now determined the structures of all supercomplexes
in mammalian mitochondria. The team is thus laying the foundation for
new treatments for mitochondrial disease.

========================================================================== Story Source: Materials provided by Institute_of_Science_and_Technology_Austria. Note: Content may be edited
for style and length.


========================================================================== Journal Reference:
1. Leonid Sazanov & Irene Vercellino. Structure and assembly of
mammalian
mitochondrial supercomplex CIII2CIV. Nature, 2021 DOI:
10.1038/s41586- 021-03927-z ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/10/211006112609.htm

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