Cell Death and Disease,
Год журнала:
2025,
Номер
16(1)
Опубликована: Март 8, 2025
Abstract
Lysosome-mediated
autophagy
(including
mitophagy)
is
crucial
for
cell
survival
and
homeostasis.
Although
the
mechanisms
of
lysosome
activation
during
stress
are
well
recognized,
epigenetic
regulation
lysosomal
gene
expression
remains
largely
unexplored.
Menin,
encoded
by
MEN1
gene,
a
chromatin-related
protein
that
widely
involved
in
transcription
via
histone
modifications.
Here,
we
report
menin
regulates
specific
genes,
such
as
CTSB
,
CTSE
TFE3
through
MLL-mediated
H3K4me3
reprogramming,
which
necessary
maintaining
Menin
also
directly
controls
SQSTM1
MAP1LC3B
to
maintain
autophagic
flux
manner
independent
AMPK/mTORC1
pathways.
Furthermore,
loss
led
mitochondrial
dysfunction,
elevated
levels
reactive
oxygen
species
(ROS),
genome
instability.
In
genetically
engineered
mouse
models,
Men1
deficiency
resulted
severe
dysfunction
an
impaired
self-clearance
ability,
further
metabolite
accumulation.
SP2509,
demethylase
inhibitor,
effectively
reversed
downregulation
genes
caused
.
Our
study
confirms
previously
unrecognized
biological
mechanistic
importance
menin-mediated
organelle
The Journal of Cell Biology,
Год журнала:
2025,
Номер
224(3)
Опубликована: Янв. 3, 2025
Many
cancer
cells
exhibit
increased
amounts
of
paucimannose
glycans,
which
are
truncated
N-glycan
structures
rarely
found
in
mammals.
Paucimannosidic
proteins
proposedly
generated
within
lysosomes
and
exposed
on
the
cell
surface
through
a
yet
uncertain
mechanism.
In
this
study,
we
revealed
that
paucimannosidic
produced
by
lysosomal
glycosidases
secreted
via
exocytosis.
Interestingly,
exocytosis
preferentially
occurred
vicinity
focal
adhesions,
protein
complexes
connecting
actin
cytoskeleton
to
extracellular
matrix.
Through
genome-wide
knockout
screening,
identified
MYO18B,
an
crosslinker,
is
required
for
adhesion
maturation,
facilitating
release
milieu.
Moreover,
mechanosensitive
cation
channel
PIEZO1
locally
activated
at
adhesions
imports
Ca2+
necessary
lysosome-plasma
membrane
fusion.
Collectively,
our
study
unveiled
intimate
relationship
between
adhesion,
shedding
light
unexpected
interplay
activities
cellular
mechanosensing.
Nature,
Год журнала:
2024,
Номер
634(8036), С. 1238 - 1244
Опубликована: Окт. 2, 2024
Lysosomes
have
crucial
roles
in
regulating
eukaryotic
metabolism
and
cell
growth
by
acting
as
signalling
platforms
to
sense
respond
changes
nutrient
energy
availability
Cell Reports,
Год журнала:
2024,
Номер
43(6), С. 114326 - 114326
Опубликована: Июнь 1, 2024
Maternal
immune
activation
is
associated
with
adverse
offspring
neurodevelopmental
outcomes,
many
mediated
by
in
utero
microglial
programming.
As
microglia
remain
inaccessible
throughout
development,
identification
of
noninvasive
biomarkers
reflecting
fetal
brain
programming
could
permit
screening
and
intervention.
We
used
lineage
tracing
to
demonstrate
the
shared
ontogeny
between
macrophages
(microglia)
placental
(Hofbauer
cells)
a
mouse
model
maternal
diet-induced
obesity,
single-cell
RNA-seq
transcriptional
programs.
Comparison
human
datasets
demonstrated
conservation
resident
macrophage
signatures
mice
humans.
Single-cell
identified
common
alterations
Hofbauer
cell
gene
expression
induced
as
well
sex
differences
these
alterations.
propose
that
cells,
which
are
easily
accessible
at
birth,
provide
insights
into
programs
may
facilitate
early
vulnerable
disorders.
Advanced Healthcare Materials,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 23, 2025
Bone
defects
caused
by
fractures
and
diseases
often
do
not
heal
spontaneously.
They
require
external
agents
for
repair
regeneration.
tissue
engineering
is
emerging
as
a
promising
alternative
to
traditional
therapies
like
autografts
allografts.
Nanobiomaterials
enhance
osteoblast
resistance
harsh
environments
promoting
cell
differentiation.
Black
phosphorus
(BP),
novel
2D
material
in
biomedicine,
displays
unique
osteogenic
antimicrobial
properties.
However,
BP
nanosheets
still
face
clinical
limitations
rapid
degradation
high-dose
cytotoxicity.
To
address
these,
the
introduction
of
amino-silicon
phthalocyanine
(SiPc-NH2)
investigated
see
if
it
can
dispersion,
reduce
oxidation,
improve
stability
safety
better
osteogenesis
antibacterial
effects
through
noncovalent
interactions
(van
der
Waals,
π-π
stacking
electrostatic
interactions).
Here,
self-healing
hydrogel
successfully
designed
using
step-by-step
co-assembly
SiPc-NH2.
SiPc-NH2
"structural
stabilizer"
reconstructed
well-dispersed
BP-SiPc-NH2
nanosheets,
which
improves
biocompatibility
BP,
reduces
oxidation
enhances
photothermal
conversion,
guaranteeing
Furthermore,
findings
show
BP-SiPc-NH2-induced
mitochondrial
changes
support
regulating
crosstalk
between
Hippo
Wnt
signaling
pathways-mediated
homeostasis,
boosting
cellular
bioenergetics.
Overall,
this
morphology-based
strategy
holds
great
promise
bone
applications.
Molecular Neurodegeneration,
Год журнала:
2024,
Номер
19(1)
Опубликована: Июнь 18, 2024
Abstract
Background
Age-related
macular
degeneration
(AMD)
is
the
leading
cause
of
blindness
in
elderly
people
developed
world,
and
number
affected
expected
to
almost
double
by
2040.
The
retina
presents
one
highest
metabolic
demands
our
bodies
that
partially
or
fully
fulfilled
mitochondria
neuroretina
retinal
pigment
epithelium
(RPE),
respectively.
Together
with
its
post-mitotic
status
constant
photooxidative
damage
from
incoming
light,
requires
a
tightly-regulated
housekeeping
system
involves
autophagy.
natural
polyphenol
Urolithin
A
(UA)
has
shown
neuroprotective
benefits
several
models
aging
age-associated
disorders,
mostly
attributed
ability
induce
mitophagy
mitochondrial
biogenesis.
Sodium
iodate
(SI)
administration
recapitulates
late
stages
AMD,
including
geographic
atrophy
photoreceptor
cell
death.
Methods
combination
vitro,
ex
vivo
were
used
test
potential
UA
SI
model.
Functional
assays
(OCT,
ERGs),
cellular
analysis
(flow
cytometry,
qPCR)
fine
confocal
microscopy
(immunohistochemistry,
tandem
selective
autophagy
reporters)
helped
address
this
question.
Results
alleviated
neurodegeneration
preserved
visual
function
SI-treated
mice.
Simultaneously,
we
observed
severe
proteostasis
defects
upon
induction,
autophagosome
accumulation,
resolved
animals
received
UA.
Treatment
restored
autophagic
flux
triggered
PINK1/Parkin-dependent
mitophagy,
as
previously
reported
literature.
Autophagy
blockage
caused
was
lysosomal
membrane
permeabilization.
While
did
not
biogenesis,
it
restore
upcycling
permeabilized
lysosomes
through
lysophagy.
Knockdown
lysophagy
adaptor
SQSTM1/p62
abrogated
viability
rescue
cells,
exacerbated
inhibited
Conclusions
Collectively,
these
data
highlight
novel
putative
application
treatment
AMD
whereby
bypasses
promoting
p62-dependent
sustain
proteostasis.
Graphical
Cells,
Год журнала:
2024,
Номер
13(16), С. 1364 - 1364
Опубликована: Авг. 16, 2024
Macroautophagy
(hereafter
autophagy)
is
a
cellular
recycling
process
that
degrades
cytoplasmic
components,
such
as
protein
aggregates
and
mitochondria,
associated
with
longevity
health
in
multiple
organisms.
While
mounting
evidence
supports
autophagy
declines
age,
the
underlying
molecular
mechanisms
remain
unclear.
Since
complex,
multistep
process,
orchestrated
by
more
than
40
autophagy-related
proteins
tissue-specific
expression
patterns
context-dependent
regulation,
it
challenging
to
determine
how
fails
age.
In
this
review,
we
describe
individual
steps
of
summarize
age-dependent
changes
reported
occur
specific
pathway
could
impact
autophagy.
Moreover,
genetic
manipulations
genes
can
affect
lifespan
healthspan
through
studies
model
organisms
age-related
disease
models.
Understanding
each
step
may
prove
useful
developing
approaches
prevent
decline
help
combat
number
diseases
dysregulated
