Abstract
The
immunoproteasome
is
a
specialized
type
of
proteasome
involved
in
MHC
class
I
antigen
presentation,
antiviral
adaptive
immunity,
autoimmunity,
and
also
part
broader
response
to
stress.
Whether
the
regulated
by
DNA
stress,
however,
not
known.
We
here
demonstrate
that
mitochondrial
stress
upregulates
presentation
pathway
via
cGAS/STING/type
interferon
signaling
resulting
cell
autonomous
activation
CD8
+
T
cells.
cGAS/STING‐induced
immune
observed
genomic
conserved
epithelial
mesenchymal
cells
mice
men.
In
patients
with
idiopathic
pulmonary
fibrosis,
chronic
aberrant
lung
concurs
T‐cell
diseased
lungs.
Genetic
depletion
specific
inhibitors
counteract
induced
cytotoxic
activation.
Our
data
thus
unravel
cytoplasmic
sensing
cGAS/STING
as
an
activator
This
represents
novel
potential
pathomechanism
for
fibrosis
opens
new
therapeutic
perspectives.
Signal Transduction and Targeted Therapy,
Год журнала:
2022,
Номер
7(1)
Опубликована: Дек. 16, 2022
Aging
is
a
gradual
and
irreversible
pathophysiological
process.
It
presents
with
declines
in
tissue
cell
functions
significant
increases
the
risks
of
various
aging-related
diseases,
including
neurodegenerative
cardiovascular
metabolic
musculoskeletal
immune
system
diseases.
Although
development
modern
medicine
has
promoted
human
health
greatly
extended
life
expectancy,
aging
society,
variety
chronic
diseases
have
gradually
become
most
important
causes
disability
death
elderly
individuals.
Current
research
on
focuses
elucidating
how
endogenous
exogenous
stresses
(such
as
genomic
instability,
telomere
dysfunction,
epigenetic
alterations,
loss
proteostasis,
compromise
autophagy,
mitochondrial
cellular
senescence,
stem
exhaustion,
altered
intercellular
communication,
deregulated
nutrient
sensing)
participate
regulation
aging.
Furthermore,
thorough
pathogenesis
to
identify
interventions
that
promote
longevity
caloric
restriction,
microbiota
transplantation,
nutritional
intervention)
clinical
treatment
methods
for
(depletion
senescent
cells,
therapy,
antioxidative
anti-inflammatory
treatments,
hormone
replacement
therapy)
could
decrease
incidence
turn
healthy
longevity.
FEBS Journal,
Год журнала:
2022,
Номер
290(5), С. 1186 - 1202
Опубликована: Янв. 20, 2022
Senescence
is
a
multi-functional
cell
fate,
characterized
by
an
irreversible
cell-cycle
arrest
and
pro-inflammatory
phenotype,
commonly
known
as
the
senescence-associated
secretory
phenotype
(SASP).
Emerging
evidence
indicates
that
accumulation
of
senescent
cells
in
multiple
tissues
drives
tissue
dysfunction
several
age-related
conditions.
This
has
spurred
academic
community
industry
to
identify
new
therapeutic
interventions
targeting
this
process.
Mitochondrial
often-unappreciated
hallmark
cellular
senescence
which
plays
important
roles
not
only
growth
but
also
development
SASP
resistance
cell-death.
Here,
we
review
supports
role
for
mitochondria
describe
underlying
mechanisms.
Finally,
propose
detailed
road
map
mitochondrial
biology
will
be
crucial
guide
future
senotherapies.
Science Signaling,
Год журнала:
2022,
Номер
15(725)
Опубликована: Март 15, 2022
The
catalytic
subunit
of
DNA-dependent
protein
kinase
(DNA-PKcs)
regulates
cell
death.
We
sought
to
determine
whether
DNA-PKcs
played
a
role
in
the
tubular
damage
that
occurs
during
acute
kidney
injury
(AKI)
induced
by
LPS
injection
(to
mimic
sepsis),
cisplatin
administration,
or
renal
ischemia/reperfusion
injury.
Although
normally
localizes
nucleus,
we
detected
cytoplasmic
mouse
tissues
and
urinary
sediments
human
patients
with
septic
AKI.
Increased
amounts
correlated
dysfunction.
Tubule
cell-specific
deletion
attenuated
AKI-mediated
death
changes
abundance
various
proteins
mitochondrial
functions
roles
apoptotic
pathways.
interacted
Fis1
phosphorylated
it
at
Thr34
its
TQ
motif,
which
increased
affinity
for
Drp1
fragmentation.
Knockin
mice
expressing
nonphosphorylatable
T34A
mutant
exhibited
improved
function
histological
features
reduced
fragmentation
upon
induction
Phosphorylation
was
detectable
AKI
Our
findings
provide
insight
into
development.
Neurons
are
highly
susceptible
to
DNA
damage
accumulation
due
their
large
energy
requirements,
elevated
transcriptional
activity,
and
long
lifespan.
While
newer
research
has
shown
that
breaks
mutations
may
facilitate
neuron
diversity
during
development
neuronal
function
throughout
life,
a
wealth
of
evidence
indicates
deficient
repair
underlies
many
neurological
disorders,
especially
age-associated
neurodegenerative
diseases.
Recently,
efforts
clarify
the
molecular
link
between
neurodegeneration
have
improved
our
understanding
how
genomic
location
defunct
proteins
impact
health.
Additionally,
work
establishing
role
for
senescence
in
aging
diseased
brain
reveals
play
central
neuroinflammation
associated
with
disease.
