Nuclear receptor subfamily 4 group A member 1 promotes myocardial ischemia/reperfusion injury through inducing mitochondrial fission factor-mediated mitochondrial fragmentation and inhibiting FUN14 domain containing 1-depedent mitophagy
International Journal of Biological Sciences,
Год журнала:
2024,
Номер
20(11), С. 4458 - 4475
Опубликована: Янв. 1, 2024
This
study
investigated
the
mechanism
by
which
NR4A1
regulates
mitochondrial
fission
factor
(Mff)-related
and
FUN14
domain
1
(FUNDC1)-mediated
mitophagy
following
cardiac
ischemia-reperfusion
injury(I/R).
Our
findings
showed
that
damage
regulation
was
positively
correlated
with
pathological
pan-apoptosis
of
myocardial
cell
mitochondria.
Compared
wild-type
mice
(WT),
NR4A1-knockout
exhibited
resistance
to
injury
fission,
characterized
activation.
Results
increased
expression
level,
activating
mediated
Mff
restoring
phenotype
FUNDC1.
The
inactivation
FUNDC1
phosphorylation
could
not
mediate
normalization
in
a
timely
manner,
leading
an
excessive
stress
response
unfolded
proteins
imbalance
homeostasis.
process
disrupted
quality
control
network,
accumulation
damaged
mitochondria
activation
pan-apoptotic
programs.
data
indicate
is
novel
critical
target
I/R
exertsand
negative
regulatory
effects
Mff-mediated
mito-fission
inhibiting
FUNDC1-mediated
mitophagy.
Targeting
crosstalk
balance
between
NR4A1-Mff-FUNDC1
potential
approach
for
treating
I/R.
Язык: Английский
Mitochondrial dysfunction in sepsis: mechanisms and therapeutic perspectives
Dongxue Hu,
Harshini Sheeja Prabhakaran,
Liang Yu
и другие.
Critical Care,
Год журнала:
2024,
Номер
28(1)
Опубликована: Сен. 3, 2024
Sepsis
is
a
severe
medical
condition
characterized
by
systemic
inflammatory
response,
often
culminating
in
multiple
organ
dysfunction
and
high
mortality
rates.
In
recent
years,
there
has
been
growing
recognition
of
the
pivotal
role
played
mitochondrial
damage
driving
progression
sepsis.
Various
factors
contribute
to
impairment
during
sepsis,
encompassing
mechanisms
such
as
reactive
nitrogen/oxygen
species
generation,
mitophagy
inhibition,
dynamics
change,
membrane
permeabilization.
Damaged
mitochondria
actively
participate
shaping
milieu
triggering
key
signaling
pathways,
including
those
mediated
Toll-like
receptors,
NOD-like
cyclic
GMP-AMP
synthase.
Consequently,
surge
interest
developing
therapeutic
strategies
targeting
mitigate
septic
pathogenesis.
This
review
aims
delve
into
intricate
underpinning
sepsis
its
significant
impact
on
immune
dysregulation.
Moreover,
we
spotlight
promising
mitochondria-targeted
interventions
that
have
demonstrated
efficacy
preclinical
models.
Язык: Английский
Activation ADORA1 protects against sepsis-associated acute kidney injury by inhibiting pyroptosis
Tissue and Cell,
Год журнала:
2025,
Номер
95, С. 102849 - 102849
Опубликована: Март 10, 2025
Язык: Английский
Galloflavin mitigates acute kidney injury by suppressing LDHA-dependent macrophage glycolysis
International Immunopharmacology,
Год журнала:
2025,
Номер
150, С. 114265 - 114265
Опубликована: Фев. 16, 2025
Macrophage-mediated
inflammation
is
closely
linked
to
the
pathogenesis
of
acute
kidney
injury
(AKI)
and
shift
macrophages
a
pro-inflammatory
phenotype
being
reliant
on
glycolytic
metabolism.
Galloflavin,
polyphenol
derived
from
tea,
functions
as
lactate
dehydrogenase
A
(LDHA)
inhibitor,
effectively
obstructing
metabolic
pathways.
However,
specific
immunometabolic
regulatory
galloflavin
in
remain
unclear.
Here,
we
observed
that
drives
alleviation
metabolism
levels
lipopolysaccharide
(LPS)-induced
(RAW264.7
cells
human
peripheral
blood
mononuclear
cells-derived
macrophages)
through
downregulation
LDHA
expression,
thereby
inhibiting
macrophage
conversion
reducing
release
inflammatory
cytokines.
overexpression
counteracts
effects
macrophages.
In
addition,
vivo
experiments
protective
effect
against
cecal
ligation
puncture
(CLP)
cisplatin-induced
renal
injury.
The
ability
inhibit
glycolysis
macrophages,
regulating
their
phenotypic
transition
during
AKI
was
further
validated
isolation
primary
This
intervention
ultimately
ameliorated
response
decelerated
progression
AKI.
Collectively,
confers
protection
by
suppressing
LDHA-dependent
mechanism,
positioning
it
potential
therapeutic
option
for
future.
Язык: Английский
Function of intramitochondrial melatonin and its association with Warburg metabolism
Cellular Signalling,
Год журнала:
2025,
Номер
unknown, С. 111754 - 111754
Опубликована: Март 1, 2025
Язык: Английский
Sepsis-Associated Acute Kidney Injury: What’s New Regarding Its Diagnostics and Therapeutics?
Diagnostics,
Год журнала:
2024,
Номер
14(24), С. 2845 - 2845
Опубликована: Дек. 17, 2024
Sepsis-associated
acute
kidney
injury
(SA-AKI)
is
defined
as
the
development
of
AKI
in
context
a
potentially
life-threatening
organ
dysfunction
attributed
to
an
abnormal
immune
response
infection.
SA-AKI
has
been
associated
with
increased
mortality
when
compared
sepsis
or
alone.
Therefore,
its
early
recognition
utmost
importance
terms
morbidity
and
rates.
The
aim
this
review
shed
light
on
pathophysiological
pathways
implicated
well
diagnostics
therapeutics.
In
review,
we
will
elucidate
upon
serum
urinary
biomarkers,
such
creatinine,
cystatin,
neutrophil
gelatinase-associated
lipocalin
(NGAL),
proenkephalin
A
119–159,
interleukin-6,
interleukin-8
interleukin-18,
soluble
toll-like
receptor
2
(sTLR2),
chemokine
ligand
(CCL2)
C-C-motif
14
(CCL14).
addition,
role
RNA
omics
machine
learning
programs
for
timely
diagnosis
be
further
discussed.
Moreover,
regarding
treatment,
elaborate
potential
therapeutic
agents
that
are
being
studied,
based
pathophysiology
SA-AKI,
humans
animal
models.
Язык: Английский