Frontiers in Oncology,
Год журнала:
2022,
Номер
12
Опубликована: Март 10, 2022
Mitochondria-related
metabolic
reprogramming
plays
a
major
role
in
the
occurrence,
development,
drug
resistance,
and
recurrence
of
acute
myeloid
leukemia
(AML).
However,
roles
mitochondria-related
genes
(MRGs)
prognosis
immune
microenvironment
for
AML
patients
remain
largely
unknown.
In
this
study,
by
least
absolute
shrinkage
selection
operator
(LASSO)
Cox
regression
analysis,
4
MRGs'
(HPDL,
CPT1A,
IDH3A,
ETFB)
signature
was
established
that
demonstrated
good
robustness
TARGET
datasets.
The
univariate
multivariate
analyses
both
MRG
robust
independent
prognostic
factor
overall
survival
prediction
with
high
accuracy
patients.
Based
on
risk
score
calculated
signature,
samples
were
divided
into
high-
low-risk
groups.
Gene
set
enrichment
analysis
(GSEA)
suggested
is
involved
immune-related
pathways.
Via
infiltration
immunosuppressive
we
found
strikingly
positively
correlated
an
cell
expression
critical
checkpoints,
indicating
poor
might
be
caused
tumor
(TME).
summary,
based
MRGs
could
act
as
predicting
clinical
also
reflect
association
microenvironment,
providing
novel
method
therapy
regulation
mitochondrial
function.
Physiological Reviews,
Год журнала:
2023,
Номер
103(4), С. 2349 - 2422
Опубликована: Апрель 6, 2023
Mitochondria
are
well
known
as
organelles
responsible
for
the
maintenance
of
cellular
bioenergetics
through
production
ATP.
Although
oxidative
phosphorylation
may
be
their
most
important
function,
mitochondria
also
integral
synthesis
metabolic
precursors,
calcium
regulation,
reactive
oxygen
species,
immune
signaling,
and
apoptosis.
Considering
breadth
responsibilities,
fundamental
metabolism
homeostasis.
Appreciating
this
significance,
translational
medicine
has
begun
to
investigate
how
mitochondrial
dysfunction
can
represent
a
harbinger
disease.
In
review,
we
provide
detailed
overview
metabolism,
bioenergetics,
dynamics,
autophagy,
damage-associated
molecular
patterns,
mitochondria-mediated
cell
death
pathways,
at
any
these
levels
is
associated
with
disease
pathogenesis.
Mitochondria-dependent
pathways
thereby
an
attractive
therapeutic
target
ameliorating
human
Frontiers in Immunology,
Год журнала:
2021,
Номер
12
Опубликована: Дек. 14, 2021
The
DNA
damage
response
(DDR)
is
an
organized
network
of
multiple
interwoven
components
evolved
to
repair
damaged
and
maintain
genome
fidelity.
Conceptually
the
DDR
includes
sensors,
transducer
kinases,
effectors
genomic
stability
accurate
transmission
genetic
information.
We
have
recently
gained
a
substantially
improved
molecular
mechanistic
understanding
how
are
interconnected
inflammatory
immune
responses
stress.
shapes
both
innate
adaptive
pathways:
(i)
in
context
immunity,
mainly
enhance
cytosolic
sensing
its
downstream
STimulator
INterferon
Genes
(STING)-dependent
signaling;
(ii)
needed
for
assembly
diversification
antigen
receptor
genes
that
requisite
T
B
lymphocyte
development.
Imbalances
between
impair
tissue
homeostasis
lead
replication
transcription
stress,
mutation
accumulation,
even
cell
death.
These
impacts
from
defects
can
then
drive
tumorigenesis,
secretion
cytokines,
aberrant
responses.
Yet,
deficiency
or
inhibition
also
directly
Furthermore,
plus
higher
load
tumor
cells
synergistically
produce
primarily
tumor-specific
neoantigens,
which
powerfully
targeted
cancer
immunotherapy
by
employing
checkpoint
inhibitors
amplify
Thus,
elucidating
DDR-immune
interplay
may
provide
critical
connections
harnessing
immunomodulatory
effects
improve
efficacy
radiation
chemotherapies,
blockade,
combined
therapeutic
strategies.
Antioxidants,
Год журнала:
2022,
Номер
11(6), С. 1151 - 1151
Опубликована: Июнь 12, 2022
Control
of
excessive
mitochondrial
oxidative
stress
could
provide
new
targets
for
both
preventive
and
therapeutic
interventions
in
the
treatment
chronic
inflammation
or
any
pathology
that
develops
under
an
inflammatory
scenario,
such
as
rheumatoid
arthritis
(RA).
Increasing
evidence
has
demonstrated
role
alterations
autoimmune
diseases
mainly
due
to
interplay
between
metabolism
innate
immunity,
but
also
modulation
response
resident
cells,
synoviocytes.
Thus,
dysfunction
derived
from
several
danger
signals
activate
tricarboxylic
acid
(TCA)
disruption,
thereby
favoring
a
vicious
cycle
oxidative/mitochondrial
stress.
Mitochondrial
can
act
through
modulating
immunity
via
redox-sensitive
pathways
direct
activation
inflammasome.
Besides,
mitochondria
have
central
regulating
cell
death,
which
is
deeply
altered
RA.
Additionally,
multiple
suggests
pathological
processes
RA
be
shaped
by
epigenetic
mechanisms
turn,
are
involved
regulation.
Finally,
we
will
discuss
about
involvement
some
dietary
components
onset
progression
Nature,
Год журнала:
2024,
Номер
628(8009), С. 844 - 853
Опубликована: Апрель 3, 2024
Abstract
Mitochondria
are
critical
modulators
of
antiviral
tolerance
through
the
release
mitochondrial
RNA
and
DNA
(mtDNA
mtRNA)
fragments
into
cytoplasm
after
infection,
activating
virus
sensors
type-I
interferon
(IFN-I)
response
1–4
.
The
relevance
these
mechanisms
for
diseases
remains
understudied.
Here
we
investigated
recessive
ataxia
syndrome
(MIRAS),
which
is
caused
by
a
common
European
founder
mutation
in
polymerase
gamma
(
POLG1
)
5
Patients
homozygous
MIRAS
variant
p.W748S
show
exceptionally
variable
ages
onset
symptoms
,
indicating
that
unknown
modifying
factors
contribute
to
disease
manifestation.
We
report
mtDNA
replicase
has
role
defence
double-stranded
positive-strand
infections
(HSV-1,
TBEV
SARS-CoV-2),
its
dampens
innate
immune
responses.
Our
patient
knock-in
mouse
data
compromises
replisome
stability,
causing
depletion,
aggravated
infection.
Low
mtRNA
slow
IFN
offer
viruses
an
early
replicative
advantage,
leading
augmented
pro-inflammatory
response,
subacute
loss
GABAergic
neurons
liver
inflammation
necrosis.
A
population
databank
around
300,000
Finnish
individuals
6
demonstrates
enrichment
immunodeficient
traits
carriers
mutation.
evidence
suggests
defects
compromise
tolerance,
triggering
epilepsy
disease.
finding
important
implications
spectrum,
including
epilepsy,
parkinsonism.
