Scientists have made an important step in understanding how
cells keep themselves clean and healthy - a finding that may have
implications for combating neurodegenerative diseases and
cancer.
One way that our bodies clean out toxic debris and damaged cell
components is by a process called autophagy, which means
'self-eating'. Our cells create internal 'recycling bins' called
autophagosomes that collect diseased, dead, or worn-out cell parts,
strips them for useful bits, and uses the resulting molecules for
energy to make new healthy cell parts. When this disposal system
stops working properly, it can lead to cancer and diseases like
Alzheimer's and Parkinson's.
Researchers at the Francis Crick Institute have uncovered a
pathway that controls autophagy, which could potentially be
targeted in future to prevent diseases. The research is published
in Current Biology.
The team had previously shown that in starved cells that need to
recycle nutrients for energy, an important protein required for
autophagy, GABARAP, moves from the centrosome - part of the cell
that contains structural scaffolds that maintain its shape and
enable cell division and movement - to the autophagosome.
In this study, they used visual markers and biochemical tools to
see how the autophagy protein gets to where it needs to be. They
found that a protein called PCM1 forms a compartment or 'centriolar
satellite' which shuttles the autophagy protein from the centrosome
to the autophagosome along a scaffold, a bit like a train carriage
transporting a person along a railway track. When they deleted the
PCM1 gene, the GABARAP autophagy protein's journey to the
autophagosome became disorganised. Some GABARAP was degraded by an
alternative recycling bin in the cell - the proteasome - and some
GABARAP went to different autophagosomes from normal, highlighting
the importance of PCM1 in controlling the assembly of the autophagy
cell machinery.
Image: Fluorescent markers highlight the autophagy machinery
inside a cell. Dark shaded area = cell nucleus; green dot cluster =
centrosome; green dots = centriolar satellites; red dots = GABARAP
in autophagosomes; yellow dots = PCM1 and GABARAP together.Credit:
Justin Joachim.
"The identification of this new type of autophagosome formed by
the disorganised GABARAP tells us that there are unique types of
autophagosomes in the cell but we don't yet understand how they
would work to prevent disease," says Sharon Tooze, Group Leader at
the Francis Crick Institute. "One of the aims of our ongoing
research is to manipulate this pathway, to boost cells' ability to
keep themselves clean and healthy."
Justin Joachim, post-doctoral fellow at the Francis Crick
Institute and first named author of the paper adds: "Our work
reveals a previously unknown connection between the centrosome,
cell division, shuttle proteins and autophagy and establishes a new
regulatory pathway to control autophagy."
The paper 'Centriolar satellites control GABARAP
ubiquitination and GABARAP-mediated autophagy' is published inCurrent Biology.