Autophagy: the beginning of the end
Scientists reveal key steps in the formation of the recycling centers of
the cell

Date:
September 4, 2020
Source:
University of Vienna
Summary:
Autophagy, from the Greek for 'self-eating', is an essential
process that isolates and recycles cellular components under
conditions of stress or when resources are limited. Scientists
have now reconstructed the first steps in the formation of
autophagosomes. They show that tiny vesicles loaded with the
protein Atg9 act as the seed from which the autophagosome emerges.



FULL STORY ========================================================================== Autophagosomes first form as cup-shaped membranes in the cell, which then
grow to engulf the cellular material designated for destruction. The
formation of these membranes is catalyzed by a complex machinery of
proteins. "We have a very good knowledge of the factors involved in autophagosomes formation," explains group leader Sascha Martens, "but
how they come together to initiate the formation of these membranes has
so far been enigmatic."

==========================================================================
One of the factors is Atg9, a protein whose importance in the process
was known, but whose role was not clear. Atg9 is found in small
intracellular vesicles. Researchers Justyna Sawa-Makarska, Verena
Baumann and Nicolas Coudevylle from the Martens lab now show that they
form a platform on which the autophagy machinery can assemble to build
the autophagosome. "Atg9 vesicles are abundant in the cell, which means
they can be rapidly recruited when autophagosomes are needed," explains
group leader Sascha Martens.

Cells encapsulate cargo in vesicles, so that they can be correctly
transported and degraded in a chemical environment that is different to
the one normally found in cells. Autophagosomes therefore consist of a
double membrane made of phospholipids. This greasy envelope creates a waterproof package that separates material from the aqueous surroundings
of the cell and marks it for degradation. However, Atg9 vesicles do not
supply the bulk of the lipids to the growing autophagosome.

To understand a complex machinery like the cell, it often helps to take it apart and rebuild it. The biogenesis of autophagosome involves numerous proteins. By isolating and characterizing 21 of these components, the scientists have been able to rebuild parts of the autophagy machinery
in the 'test tube' -- an arduous process that took Sascha Martens and
his team almost ten years. "With this approach we could reconstitute
the early steps of autophagosome biogenesis in a controlled manner,"
he says. With the elaborate toolkit the Martens lab has developed,
the scientists now aim to unravel the next steps in the biogene-sis
of the autophagosome. The research project was a collaboration of the
Martens lab with Gerhard Hummer and Soeren von Bu"low from the Max
Planck Institute for Biophysics in Frankfurt and Martin Graef from the
Max Planck Institute for Biology of Ageing in Cologne.


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


========================================================================== Journal Reference:
1. Justyna Sawa-Makarska, Verena Baumann, Nicolas Coudevylle,
So"ren von
Bu"low, Veronika Nogellova, Christine Abert, Martina Schuschnig,
Martin Graef, Gerhard Hummer, Sascha Martens. Reconstitution
of autophagosome nucleation defines Atg9 vesicles as seeds for
membrane formation.

Science, 2020; 369 (6508): eaaz7714 DOI: 10.1126/science.aaz7714 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/09/200904121335.htm

--- up 1 week, 4 days, 6 hours, 50 minutes
* Origin: -=> Castle Rock BBS <=- Now Husky HPT Powered! (1337:3/111)