Immunity,
Год журнала:
2022,
Номер
55(8), С. 1370 - 1385.e8
Опубликована: Июль 13, 2022
Mitochondrial
DNA
(mtDNA)
escaping
stressed
mitochondria
provokes
inflammation
via
cGAS-STING
pathway
activation
and,
when
oxidized
(Ox-mtDNA),
it
binds
cytosolic
NLRP3,
thereby
triggering
inflammasome
activation.
However,
is
unknown
how
and
in
which
form
Ox-mtDNA
exits
non-apoptotic
macrophages.
We
found
that
diverse
NLRP3
activators
rapidly
stimulated
uniporter-mediated
calcium
uptake
to
open
mitochondrial
permeability
transition
pores
(mPTP)
trigger
VDAC
oligomerization.
This
occurred
independently
of
mtDNA
or
reactive
oxygen
species,
induce
generation.
Within
mitochondria,
was
either
repaired
by
glycosylase
OGG1
cleaved
the
endonuclease
FEN1
500–650
bp
fragments
exited
mPTP-
VDAC-dependent
channels
initiate
also
activated
signaling
gave
rise
pro-inflammatory
extracellular
DNA.
Understanding
this
process
will
advance
development
potential
treatments
for
chronic
inflammatory
diseases,
exemplified
inhibitors
suppressed
interleukin-1β
(IL-1β)
production
release
mice.
Cell Research,
Год журнала:
2019,
Номер
29(5), С. 347 - 364
Опубликована: Апрель 4, 2019
Cells
may
die
from
accidental
cell
death
(ACD)
or
regulated
(RCD).
ACD
is
a
biologically
uncontrolled
process,
whereas
RCD
involves
tightly
structured
signaling
cascades
and
molecularly
defined
effector
mechanisms.
A
growing
number
of
novel
non-apoptotic
forms
have
been
identified
are
increasingly
being
implicated
in
various
human
pathologies.
Here,
we
critically
review
the
current
state
art
regarding
types
RCD,
including
necroptosis,
pyroptosis,
ferroptosis,
entotic
death,
netotic
parthanatos,
lysosome-dependent
autophagy-dependent
alkaliptosis
oxeiptosis.
The
in-depth
comprehension
each
these
lethal
subroutines
their
intercellular
consequences
uncover
therapeutic
targets
for
avoidance
pathogenic
loss.
Frontiers in Cell and Developmental Biology,
Год журнала:
2021,
Номер
9
Опубликована: Март 29, 2021
Cellular
senescence
is
a
stable
cell
cycle
arrest
that
can
be
triggered
in
normal
cells
response
to
various
intrinsic
and
extrinsic
stimuli,
as
well
developmental
signals.
Senescence
considered
highly
dynamic,
multi-step
process,
during
which
the
properties
of
senescent
continuously
evolve
diversify
context
dependent
manner.
It
associated
with
multiple
cellular
molecular
changes
distinct
phenotypic
alterations,
including
proliferation
unresponsive
mitogenic
stimuli.
Senescent
remain
viable,
have
alterations
metabolic
activity
undergo
dramatic
gene
expression
develop
complex
senescence-associated
secretory
phenotype.
compromise
tissue
repair
regeneration,
thereby
contributing
toward
aging.
Removal
attenuate
age-related
dysfunction
extend
health
span.
also
act
potent
anti-tumor
mechanism,
by
preventing
potentially
cancerous
cells.
program
acts
double-edged
sword,
both
beneficial
detrimental
effects
on
organism,
an
example
evolutionary
antagonistic
pleiotropy.
Activation
p53/p21
WAF1/CIP1
p16
INK4A
/pRB
tumor
suppressor
pathways
play
central
role
regulating
senescence.
Several
other
recently
been
implicated
mediating
Herein
we
review
mechanisms
underlie
growth
particular
focus
why
stop
dividing,
stability
arrest,
hypersecretory
phenotype
how
different
are
all
integrated.
Cancer Discovery,
Год журнала:
2019,
Номер
10(1), С. 26 - 39
Опубликована: Дек. 18, 2019
The
recognition
of
DNA
as
an
immune-stimulatory
molecule
is
evolutionarily
conserved
mechanism
to
initiate
rapid
innate
immune
responses
against
microbial
pathogens.
cGAS-STING
pathway
was
discovered
important
DNA-sensing
machinery
in
immunity
and
viral
defense.
Recent
advances
have
now
expanded
the
roles
cancer.
Highly
aggressive,
unstable
tumors
evolved
co-opt
this
program
drive
tumorigenic
behaviors.
In
review,
we
discuss
link
between
antitumor
well
cancer
progression,
genomic
instability,
tumor
microenvironment,
pharmacologic
strategies
for
therapy.
SIGNIFICANCE:
defense
infections.
Given
its
role
activating
surveillance,
it
has
been
assumed
that
primarily
functions
a
suppressor.
Yet,
mounting
evidence
suggests
depending
on
context,
signaling
can
also
metastasis-promoting
functions,
chronic
activation
paradoxically
induce
immune-suppressive
microenvironment.
