Autophagy,
Год журнала:
2024,
Номер
20(7), С. 1471 - 1472
Опубликована: Май 14, 2024
The
destination
of
a
damaged
lysosome
is
either
being
repaired
if
the
damage
small
or
degraded
through
lysosome-specific
macroautophagy/autophagy
pathway
named
lysophagy
when
too
extensive
to
repair.
Even
though
previous
studies
report
lumenal
glycan
exposure
during
as
signal
trigger
lysophagy,
it
possibly
beneficial
for
cells
initiate
earlier
than
membrane
rupture.
In
recently
published
article,
Gahlot
et
al.
determined
that
SPART/SPG20
senses
lipid-packing
defects
and
recruits
activates
ubiquitin
ligase
ITCH,
which
labels
lysosomes
with
chains
lysophagy.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Июнь 8, 2024
Based
on
genetic
studies,
lysosome
dysfunction
is
thought
to
play
a
pathogenetic
role
in
Parkinson's
disease
(PD).
Here
we
show
that
VPS13C,
bridge-like
lipid
transport
protein
and
PD
gene,
sensor
of
stress/damage.
Upon
membrane
perturbation,
VPS13C
rapidly
relocates
from
the
cytosol
surface
lysosomes
where
it
tethers
their
membranes
ER.
This
recruitment
depends
Rab7
requires
signal
at
damaged
releases
an
inhibited
state
which
hinders
access
its
VAB
domain
lysosome-bound
Rab7.
While
another
protein,
LRRK2,
also
recruited
stressed/damaged
lysosomes,
occurs
much
later
stages
by
different
mechanisms.
Given
VPS13
proteins
bulk
transport,
these
findings
suggest
delivery
part
early
protective
response
damage.
The Journal of Cell Biology,
Год журнала:
2025,
Номер
224(6)
Опубликована: Апрель 9, 2025
The
transmembrane
autophagy
protein
ATG9
has
multiple
functions
essential
for
autophagosome
formation.
Here,
we
uncovered
a
novel
function
of
ATG-9
in
regulating
lysosome
biogenesis
and
integrity
Caenorhabditis
elegans.
Through
genetic
screen,
identified
that
mutations
attenuating
the
lipid
scrambling
activity
suppress
defect
epg-5
mutants,
which
non-degradative
autolysosomes
accumulate.
scramblase-attenuated
mutants
promote
delivery
lysosome-localized
hydrolases
also
facilitate
maintenance
integrity.
manipulation
phospholipid
levels,
found
reduction
phosphatidylethanolamine
(PE)
suppresses
defects
damage
associated
with
impaired
lysosomal
degradation.
Our
results
reveal
modulation
composition
distribution,
e.g.,
by
scramblase
or
reducing
PE
level,
regulates
Healthy
cells
need
functional
lysosomes
to
degrade
cargo
delivered
by
autophagy
and
endocytosis.
Defective
can
lead
severe
conditions
such
as
lysosomal
storage
diseases
(LSDs)
neurodegeneration.
To
maintain
lysosome
integrity
functionality,
have
evolved
multiple
quality
control
pathways
corresponding
different
types
of
stress
damage.
These
be
divided
into
five
levels:
regulation,
reformation,
repair,
removal,
replacement.
The
levels
often
work
together
the
network.
This
review
summarizes
discusses
less-studied
area
membrane
protein
regulation
degradation,
highlighting
key
unanswered
questions
in
field.
Cellular & Molecular Biology Letters,
Год журнала:
2024,
Номер
29(1)
Опубликована: Сен. 5, 2024
Abstract
Lysosomes
are
acidic
organelles
involved
in
crucial
intracellular
functions,
including
the
degradation
of
and
protein,
membrane
repair,
phagocytosis,
endocytosis,
nutrient
sensing.
Given
these
key
roles
lysosomes,
maintaining
their
homeostasis
is
essential
for
cell
viability.
Thus,
to
preserve
lysosome
integrity
functionality,
cells
have
developed
a
complex
system,
called
quality
control
(LQC).
Several
stressors
may
affect
causing
Lysosomal
permeabilization
(LMP),
which
rupture
results
leakage
luminal
hydrolase
enzymes
into
cytosol.
After
sensing
damage,
LQC
either
activates
or
induces
ruptured
lysosomes
through
autophagy.
In
addition,
stimulates
de
novo
biogenesis
functional
exocytosis.
Alterations
give
rise
deleterious
consequences
cellular
homeostasis.
Specifically,
persistence
impaired
malfunctioning
lysosomal
processes
leads
toxicity
death,
thereby
contributing
pathogenesis
different
disorders,
neurodegenerative
diseases
(NDs).
Recently,
several
pieces
evidence
underlined
importance
role
NDs.
this
review,
we
describe
elements
how
they
cooperate
maintain
homeostasis,
implication
Graphical
Cells,
Год журнала:
2024,
Номер
13(20), С. 1675 - 1675
Опубликована: Окт. 10, 2024
The
epidermis
of
the
skin
and
appendages,
such
as
nails,
hair
sebaceous
glands,
depend
on
a
balance
cell
proliferation
terminal
differentiation
in
order
to
fulfill
their
functions
at
interface
body
environment.
epithelial
cells
skin,
commonly
referred
keratinocytes,
involves
major
remodeling
processes
that
generate
metabolically
inactive
remnants
serving
building
blocks
epidermal
stratum
corneum,
nail
plates
shafts.
Only
gland
results
disintegration
holocrine
secretion.
A
series
studies
performed
past
decade
have
revealed
lysosome-dependent
intracellular
degradation
mechanism
autophagy
is
active
during
keratinocyte
differentiation,
blockade
significantly
alters
properties
products.
Here,
we
present
model
for
autophagy-mediated
organelles
cytosolic
proteins
an
important
contributor
cellular
differentiation.
roles
are
discussed
comparison
alternative
mechanisms
context
programmed
death
integral
end
point
Lysosomal
pH
dysregulation
is
a
critical
element
of
the
pathophysiology
neurodegenerative
diseases,
cancers,
and
lysosomal
storage
disorders
(LSDs).
To
study
role
lysosomes
in
pathophysiology,
probes
to
analyze
size,
positioning,
are
indispensable
tools.
Here,
we
developed
characterized
ratiometric
genetically
encoded
probe,
RpH-ILV,
targeted
subpopulation
intraluminal
vesicles.
This
behaves
similarly
general
population
LAMP1-positive
vesicles
terms
response
pharmacological
stresses.
In
addition,
which
trafficked
lysosome
via
different
cytosolic
motif
than
our
previous
sensor,
RpH-LAMP1,
well
tolerated
by
model
organism
Drosophila
melanogaster
,
exhibits
minimal
plasma
membrane
fluorescence,
reveals
sensitivity
damaging
agent
LLOMe,
adding
valuable
tool
repertoire
sensors.
