Nature Communications,
Год журнала:
2021,
Номер
12(1)
Опубликована: Фев. 23, 2021
Abstract
Upon
starvation,
cells
rewire
their
metabolism,
switching
from
glucose-based
metabolism
to
mitochondrial
oxidation
of
fatty
acids,
which
require
the
transfer
FAs
lipid
droplets
(LDs)
mitochondria
at
mitochondria−LD
membrane
contact
sites
(MCSs).
However,
factors
responsible
for
FA
these
MCSs
remain
uncharacterized.
Here,
we
demonstrate
that
vacuolar
protein
sorting-associated
13D
(VPS13D),
loss-of-function
mutations
cause
spastic
ataxia,
coordinates
trafficking
in
conjunction
with
endosomal
sorting
complex
required
transport
(ESCRT)
tumor
susceptibility
101
(TSG101).
The
VPS13
adaptor-binding
domain
VPS13D
and
TSG101
directly
remodels
LD
membranes
a
cooperative
manner.
human
binds
glycerophospholipids
vitro.
Depletion
VPS13D,
TSG101,
or
ESCRT-III
proteins
inhibits
LDs
mitochondria.
Our
findings
suggest
mediates
ESCRT-dependent
remodeling
facilitate
mitochondria-LD
contacts.
Autophagy,
Год журнала:
2021,
Номер
17(1), С. 1 - 382
Опубликована: Янв. 2, 2021
In
2008,
we
published
the
first
set
of
guidelines
for
standardizing
research
in
autophagy.
Since
then,
this
topic
has
received
increasing
attention,
and
many
scientists
have
entered
field.
Our
knowledge
base
relevant
new
technologies
also
been
expanding.
Thus,
it
is
important
to
formulate
on
a
regular
basis
updated
monitoring
autophagy
different
organisms.
Despite
numerous
reviews,
there
continues
be
confusion
regarding
acceptable
methods
evaluate
autophagy,
especially
multicellular
eukaryotes.
Here,
present
investigators
select
interpret
examine
related
processes,
reviewers
provide
realistic
reasonable
critiques
reports
that
are
focused
these
processes.
These
not
meant
dogmatic
rules,
because
appropriateness
any
assay
largely
depends
question
being
asked
system
used.
Moreover,
no
individual
perfect
every
situation,
calling
use
multiple
techniques
properly
monitor
each
experimental
setting.
Finally,
several
core
components
machinery
implicated
distinct
autophagic
processes
(canonical
noncanonical
autophagy),
implying
genetic
approaches
block
should
rely
targeting
two
or
more
autophagy-related
genes
ideally
participate
steps
pathway.
Along
similar
lines,
proteins
involved
regulate
other
cellular
pathways
including
apoptosis,
all
them
can
used
as
specific
marker
bona
fide
responses.
critically
discuss
current
assessing
information
they
can,
cannot,
provide.
ultimate
goal
encourage
intellectual
technical
innovation
The Journal of Cell Biology,
Год журнала:
2019,
Номер
218(6), С. 1787 - 1798
Опубликована: Апрель 5, 2019
During
macroautophagic
stress,
autophagosomes
can
be
produced
continuously
and
in
high
numbers.
Many
different
organelles
have
been
reported
as
potential
donor
membranes
for
this
sustained
autophagosome
growth,
but
specific
machinery
to
support
the
delivery
of
lipid
growing
membrane
has
remained
unknown.
Here
we
show
that
autophagy
protein,
ATG2,
without
a
clear
function
since
its
discovery
over
20
yr
ago,
is
fact
lipid-transfer
protein
likely
operating
at
ER-autophagosome
interface.
ATG2A
bind
tens
glycerophospholipids
once
transfers
lipids
robustly
vitro.
An
N-terminal
fragment
supports
transfer
vitro
both
necessary
fully
sufficient
rescue
blocked
biogenesis
ATG2A/ATG2B
KO
cells,
implying
regulation
homeostasis
major
autophagy-dependent
activity
and,
by
extension,
protein-mediated
across
contact
sites
principal
contributor
formation.
An
enigmatic
step
in
de
novo
formation
of
the
autophagosome
membrane
compartment
is
expansion
precursor
phagophore,
which
requires
acquisition
lipids
to
serve
as
building
blocks.
Autophagy-related
2
(ATG2),
rod-shaped
protein
that
tethers
phosphatidylinositol
3-phosphate
(PI3P)-enriched
phagophores
endoplasmic
reticulum
(ER),
suggested
be
essential
for
phagophore
expansion,
but
underlying
mechanism
remains
unclear.
Here,
we
demonstrate
human
ATG2A
a
lipid
transfer
protein.
can
extract
from
vesicles
and
unload
them
other
vesicles.
Lipid
by
more
efficient
between
tethered
than
untethered
The
PI3P
effectors
WIPI4
WIPI1
associate
stably
PI3P-containing
vesicles,
thereby
facilitating
ATG2A-mediated
tethering
PI3P-free
Based
on
these
results,
propose
ATG2-mediated
ER
enables
expansion.
The Journal of Cell Biology,
Год журнала:
2020,
Номер
219(6)
Опубликована: Май 1, 2020
Autophagosome
biogenesis
involves
de
novo
formation
of
a
membrane
that
elongates
to
sequester
cytoplasmic
cargo
and
closes
form
double-membrane
vesicle
(an
autophagosome).
This
process
has
remained
enigmatic
since
its
initial
discovery
>50
yr
ago,
but
our
understanding
the
mechanisms
involved
in
autophagosome
increased
substantially
during
last
20
yr.
Several
key
questions
do
remain
open,
however,
including,
What
determines
site
nucleation?
is
origin
lipid
composition
membrane?
How
sequestration
regulated
under
nonselective
selective
types
autophagy?
review
provides
insight
into
core
molecular
underlying
biogenesis,
with
specific
emphasis
on
modeling
events,
highlights
recent
conceptual
advances
field.
Annual Review of Cell and Developmental Biology,
Год журнала:
2019,
Номер
35(1), С. 477 - 500
Опубликована: Июль 24, 2019
Autophagy
is
the
major
cellular
pathway
to
degrade
dysfunctional
organelles
and
protein
aggregates.
particularly
important
in
neurons,
which
are
terminally
differentiated
cells
that
must
last
lifetime
of
organism.
There
both
constitutive
stress-induced
pathways
for
autophagy
catalyze
turnover
aged
or
damaged
mitochondria,
endoplasmic
reticulum,
other
organelles,
aggregated
proteins.
These
required
neurodevelopment
as
well
maintenance
neuronal
homeostasis.
Here
we
review
core
components
autophagosome
biogenesis,
cell
biology
bulk
selective
neurons.
Finally,
discuss
role
development,
homeostasis,
aging
links
between
deficits
neurodegeneration.
