Cell Death Discovery,
Год журнала:
2023,
Номер
9(1)
Опубликована: Ноя. 25, 2023
During
the
process
of
wound
healing,
fibroblasts
migrate
to
site
and
perform
essential
functions
in
promoting
cell
proliferation,
as
well
synthesizing
secreting
extracellular
matrix
(ECM).
However,
diabetic
wounds,
senescent
exhibit
impaired
proliferative
capacity
fail
synthesize
ECM
components.
Pyruvate
dehydrogenase
kinase
4
(PDK4),
a
key
enzyme
regulating
energy
metabolism,
has
been
implicated
modulating
cellular
senescence
fibroblast
function.
its
specific
role
wounds
remains
poorly
understood.
In
this
study,
we
conducted
series
vivo
vitro
experiments
using
STZ-induced
mice
human
dermal
fibroblasts.
We
evaluated
markers,
including
SA-β-gal,
P53,
P16,
P21,
PAI-1,
senescence-associated
secretory
phenotype
(SASP)
factors.
Finally,
observed
that
PDK4
increased
normal
but
expression
was
insufficient
wounds.
Significantly,
overexpression
demonstrated
potential
accelerate
healing
improve
both
vitro.
Furthermore,
our
study
elucidated
underlying
mechanism
by
which
improved
through
enhancement
glycolysis
regulation
YAP
JNK
pathway.
The
effect
dependent
on
metabolic
reprogramming
subsequent
reduction
reactive
oxygen
species
(ROS),
mediated
PDK4.
Overall,
findings
highlight
promising
therapeutic
target
for
addressing
Frontiers in Immunology,
Год журнала:
2022,
Номер
13
Опубликована: Авг. 1, 2022
Ferroptosis
is
a
phospholipid
peroxidation-mediated
and
iron-dependent
cell
death
form,
involved
in
sepsis-induced
organ
injury
other
lung
diseases.
Yes-associated
protein
1
(YAP1),
key
regulator
of
the
Hippo
signaling
pathway,
could
target
multiple
ferroptosis
regulators.
Herein,
this
study
aimed
to
explore
involvement
etiopathogenesis
acute
(ALI)
demonstrate
that
YAP1
disrupt
ferritinophagy
moderate
ALI.
Cecal
ligation
puncture
(CLP)
models
were
constructed
wild-type
(WT)
pulmonary
epithelium-conditional
knockout
(YAP1
f/f
)
mice
induce
ALI,
while
MLE-12
cells
with
or
without
overexpression
stimulated
by
lipopolysaccharide
(LPS)
vitro
.
In-vivo
modes
showed
aggravated
CLP-induced
ALI
also
accelerated
ferroptosis,
as
presented
downregulated
expression
GPX4,
FTH1,
SLC7A11,
along
upregulated
SFXN1
NCOA4.
Transcriptome
research
identified
these
genes
pathways
In-vitro
consistently
verified
deficiency
boosted
ferrous
iron
accumulation
mitochondrial
dysfunction
response
LPS.
Furthermore,
co-IP
assay
revealed
prevent
degradation
ferritin
mass
Fe
2+
(ferritinophagy)
via
disrupting
NCOA4–FTH1
interaction,
which
blocked
transport
cytoplasmic
into
mitochondria
membrane
(SFXN1),
further
reducing
generation
ROS.
Therefore,
findings
inhibit
ferritinophagy-mediated
manner,
thus
alleviating
may
provide
new
approach
therapeutic
orientation
for
Molecular Biomedicine,
Год журнала:
2023,
Номер
4(1)
Опубликована: Окт. 16, 2023
Abstract
Ferroptosis,
a
regulated
form
of
cellular
death
characterized
by
the
iron-mediated
accumulation
lipid
peroxides,
provides
novel
avenue
for
delving
into
intersection
metabolism,
oxidative
stress,
and
disease
pathology.
We
have
witnessed
mounting
fascination
with
ferroptosis,
attributed
to
its
pivotal
roles
across
diverse
physiological
pathological
conditions
including
developmental
processes,
metabolic
dynamics,
oncogenic
pathways,
neurodegenerative
cascades,
traumatic
tissue
injuries.
By
unraveling
intricate
underpinnings
molecular
machinery,
contributors,
signaling
conduits,
regulatory
networks
governing
researchers
aim
bridge
gap
between
intricacies
this
unique
mode
multifaceted
implications
health
disease.
In
light
rapidly
advancing
landscape
ferroptosis
research,
we
present
comprehensive
review
aiming
at
extensive
in
origins
progress
human
diseases.
This
concludes
careful
analysis
potential
treatment
approaches
carefully
designed
either
inhibit
or
promote
ferroptosis.
Additionally,
succinctly
summarized
therapeutic
targets
compounds
that
hold
promise
targeting
within
various
facet
underscores
burgeoning
possibilities
manipulating
as
strategy.
summary,
enriched
insights
both
investigators
practitioners,
while
fostering
an
elevated
comprehension
latent
translational
utilities.
revealing
basic
processes
investigating
possibilities,
crucial
resource
scientists
medical
aiding
deep
understanding
effects
situations.
Drug
resistance
is
a
common
challenge
in
clinical
tumor
treatment.
A
reduction
drug
sensitivity
of
cells
often
accompanied
by
an
increase
autophagy
levels,
leading
to
autophagy-related
resistance.
The
effectiveness
combining
chemotherapy
drugs
with
inducers/inhibitors
has
been
widely
confirmed,
but
the
mechanisms
are
still
unclear.
Ferroptosis
and
pyroptosis
can
be
affected
various
types
autophagy.
Therefore,
ferroptosis
have
crosstalk
via
autophagy,
potentially
switch
cell
death
under
certain
conditions.
As
two
forms
inflammatory
programmed
death,
different
effects
on
inflammation,
cGAS-STING
signaling
pathway
also
involved.
it
plays
important
role
progression
some
chronic
diseases.
This
review
discusses
relationship
between
pyroptosis,
attempts
uncover
reasons
behind
evasion
nature
Abstract
Background
The
liver
plays
crucial
roles
in
sepsis
and
is
one
of
the
major
targets
for
sepsis-related
injuries.
Ferroptosis,
a
newly
emerged
form
lytic
cell
death,
has
been
implicated
related
organ
failure.
Yes-associated
protein1
(YAP1),
key
regulator
Hippo
signaling
pathway,
may
be
involved
ferroptosis
development.
This
study
aimed
to
elucidate
role
YAP1
septic
injury
through
regulating
ferroptosis,
especially
ferritinophagy-mediated
ferroptosis.
Results
Cecal
ligation
puncture
(CLP)
models
were
constructed
control
(
Yap1
flfl
)
liver-conditional
knockout
mice
fl/fl
Alb-Cre)
induce
injury,
while
LO2
cells
with
or
without
overexpression/deletion
stimulated
by
lipopolysaccharide
(LPS)
vitro.
Our
showed
knockdown
aggravated
CLP-induced
inflammation,
as
well
accelerated
hepatocyte
revealed
down-regulated
expression
GPX4,
FTH1
SLC7A11,
along
up-regulated
SFXN1
NCOA4.
Consistently,
deficiency
but
overexpression
alleviated
LPS-induced
ferritinophagy,
evidenced
reduced
mitochondrial
ROS
Fe
2+
,
Further
co-IP
assay
verified
that
disrupted
interaction
between
NCOA4
FTH1,
thus
prevent
degradation
ferritin
further
production
suppressed
Conclusion
inhibits
hepatocytes,
aggravates
sepsis-induced
injury.
Frontiers in Pharmacology,
Год журнала:
2022,
Номер
13
Опубликована: Окт. 21, 2022
Ferritinophagy,
a
form
of
autophagy,
is
also
an
important
part
ferroptosis,
type
regulated
cell
death
resulting
from
abnormal
iron
metabolism
involving
the
production
reactive
oxygen
species.
As
autophagy
and
cancer
have
been
revealed,
ferritinophagy
has
attracted
increasing
attention
in
development.
In
this
review,
we
discuss
latest
research
progress
on
autophagy-associated
ferroptosis
led
by
ferritinophagy,
regulators
promising
treatments
that
target
ferritinophagy.
Ferritinophagy
at
intersection
plays
significant
role
The
discussed
studies
provide
new
insights
into
mechanisms
related
for
cancer.
Redox Biology,
Год журнала:
2024,
Номер
73, С. 103195 - 103195
Опубликована: Май 17, 2024
Accumulating
oxidative
damage
is
a
primary
driver
of
ovarian
reserve
decline
along
with
aging.
However,
the
mechanism
behind
imbalance
in
reactive
oxygen
species
(ROS)
not
yet
fully
understood.
Here
we
investigated
changes
iron
metabolism
and
its
relationship
ROS
disorder
aging
ovaries
mice.
We
found
increased
content
oocytes,
abnormal
expression
metabolic
proteins,
including
heme
oxygenase
1
(HO-1),
ferritin
heavy
chain
(FTH),
light
(FTL),
mitochondrial
(FTMT),
divalent
metal
transporter
(DMT1),
ferroportin1(FPN1),
regulatory
proteins
(IRP1
IRP2)
transferrin
receptor
(TFR1).
Notably,
oocytes
exhibited
enhanced
ferritinophagy
mitophagy,
consistently,
there
was
an
increase
cytosolic
Fe2+,
elevated
lipid
peroxidation,
dysfunction,
augmented
lysosome
activity.
Additionally,
p53,
p21,
p16
microtubule-associated
protein
tau
(Tau)
were
also
to
be
upregulated.
These
alterations
could
phenocopied
vitro
Fe2+
administration
from
2-month-old
mice
but
alleviated
by
deferoxamine
(DFO).
In
vivo
application
DFO
improved
redox
status
12-month-old
mice,
corrected
Fe
