Mitochondria at the crossroads of health and disease
Cell,
Год журнала:
2024,
Номер
187(11), С. 2601 - 2627
Опубликована: Май 1, 2024
Mitochondria
reside
at
the
crossroads
of
catabolic
and
anabolic
metabolism—the
essence
life.
How
their
structure
function
are
dynamically
tuned
in
response
to
tissue-specific
needs
for
energy,
growth
repair,
renewal
is
being
increasingly
understood.
respond
intrinsic
extrinsic
stresses
can
alter
cell
organismal
by
inducing
metabolic
signaling
within
cells
distal
tissues.
Here,
we
review
how
centrality
mitochondrial
functions
manifests
health
a
broad
spectrum
diseases
aging.
Язык: Английский
Mitochondrial diseases: from molecular mechanisms to therapeutic advances
Signal Transduction and Targeted Therapy,
Год журнала:
2025,
Номер
10(1)
Опубликована: Янв. 9, 2025
Abstract
Mitochondria
are
essential
for
cellular
function
and
viability,
serving
as
central
hubs
of
metabolism
signaling.
They
possess
various
metabolic
quality
control
mechanisms
crucial
maintaining
normal
activities.
Mitochondrial
genetic
disorders
can
arise
from
a
wide
range
mutations
in
either
mitochondrial
or
nuclear
DNA,
which
encode
proteins
other
contents.
These
defects
lead
to
breakdown
metabolism,
such
the
collapse
oxidative
phosphorylation,
one
mitochondria’s
most
critical
functions.
diseases,
common
group
disorders,
characterized
by
significant
phenotypic
heterogeneity.
Clinical
symptoms
manifest
systems
organs
throughout
body,
with
differing
degrees
forms
severity.
The
complexity
relationship
between
mitochondria
diseases
results
an
inadequate
understanding
genotype-phenotype
correlation
these
historically
making
diagnosis
treatment
challenging
often
leading
unsatisfactory
clinical
outcomes.
However,
recent
advancements
research
technology
have
significantly
improved
our
management
conditions.
translations
mitochondria-related
therapies
actively
progressing.
This
review
focuses
on
physiological
mitochondria,
pathogenesis
potential
diagnostic
therapeutic
applications.
Additionally,
this
discusses
future
perspectives
diseases.
Язык: Английский
A safety and absolute activity measurement method for Phi29 DNA polymerase based on chemiluminescent detection of dATP consumption
Analytica Chimica Acta,
Год журнала:
2025,
Номер
unknown, С. 343952 - 343952
Опубликована: Март 1, 2025
Язык: Английский
Genetic Landscape and Mitochondrial Metabolic Dysregulation in Patients Suffering From Severe Long COVID
Journal of Medical Virology,
Год журнала:
2025,
Номер
97(3)
Опубликована: Март 1, 2025
ABSTRACT
Long
COVID
represents
a
significant
global
health
challenge
with
an
unclear
etiology.
Alongside
accumulating
evidence
of
mitochondrial
dysfunction
in
patients
acute
SARS‐CoV‐2
infection,
symptomatic
overlap
exists
between
long
and
disorders.
However,
the
genetic
underpinnings
have
not
been
previously
explored.
We
employed
whole
genome
sequencing
to
analyze
13
severe
identify
defects
related
function.
performed
extracellular
bioenergetics
flux
analysis
on
peripheral
blood
mononuclear
cells
proteomics
evaluate
cellular
compared
results
those
healthy
controls.
Our
investigation
identified
10
variants
classified
as
pathogenic
or
likely
83
unknown
significance
affecting
wide
range
mitochondria‐associated
biological
functions.
Bioenergetics
revealed
altered
ATP
production
rate
four
This
study
presents
initial
potential
underlying
predisposition
while
demonstrating
energy
capacity
subset
these
patients.
These
findings
open
avenues
for
further
research
into
role
pathology
suffering
from
may
pave
way
targeted
therapeutic
strategies
aimed
at
mitigating
dysfunction.
Язык: Английский
Interferon Stimulated Gene Expression Is a Biomarker for Primary Mitochondrial Disease
Annals of Neurology,
Год журнала:
2024,
Номер
unknown
Опубликована: Сен. 25, 2024
Objective
Mitochondria
are
implicated
in
regulation
of
the
innate
immune
response.
We
hypothesized
that
abnormalities
interferon
signaling
may
contribute
to
pathophysiology
patients
with
primary
mitochondrial
disease
(PMD).
Methods
Expression
stimulated
genes
(ISGs)
was
measured
by
real‐time
polymerase
chain
reaction
(PCR)
whole
blood
samples
from
a
cohort
PMD.
Results
Upregulated
ISG
expression
observed
high
proportion
(41/55,
75%)
PMD
on
at
least
1
occasion,
most
frequently
IFI27
upregulation,
seen
50%
samples.
Some
had
extremely
levels,
similar
those
interferonopathies.
A
statistically
significant
correlation
between
elevated
gene
and
PMD,
but
not
secondary
dysfunction,
suggesting
upregulation
is
biomarker
In
some
persisted
repeat
measurement
over
several
years,
indicative
ongoing
chronic
inflammation.
Subgroup
analyses
suggested
common
signatures
mechanisms
positive
correlations
severity
among
identical
genetic
diagnoses.
Interpretation
Dysregulated
dysregulation
contributor
pathophysiology.
This
indicate
role
for
repurposing
immunomodulatory
therapies
treatment
PMDs
targeting
signaling.
ANN
NEUROL
2024
Язык: Английский
An updated review of HSV-1 infection-associated diseases and treatment, vaccine development, and vector therapy application
Virulence,
Год журнала:
2024,
Номер
15(1)
Опубликована: Ноя. 7, 2024
Herpes
simplex
virus
type
1
(HSV-1)
is
a
globally
widespread
that
causes
and
associates
with
wide
range
of
diseases,
including
herpes
encephalitis,
keratitis,
labialis.
The
interaction
between
HSV-1
the
host
involves
complex
immune
response
mechanisms,
recognition
viral
invasion,
maintenance
latent
infection,
triggering
reactivation.
Antiviral
therapy
core
treatment
for
infections.
Meanwhile,
vaccine
development
employs
different
strategies
methods,
several
promising
types
have
emerged,
such
as
live
attenuated,
protein
subunit,
nucleic
acid
vaccines,
offering
new
possibilities
prevention
infection.
Moreover,
can
be
modified
into
therapeutic
vector
gene
tumour
immunotherapy.
This
review
provides
an
in-depth
summary
infection-associated
innate
adaptive
responses,
disease
pathogenesis,
current
approaches,
recent
advances
in
development,
applications
cancer
treatment.
Through
systematic
multiple
aspects
HSV-1,
this
study
aims
to
provide
comprehensive
detailed
reference
public
on
prevention,
control,
HSV-1.
Язык: Английский
Caspase-11 drives macrophage hyperinflammation in models of Polg-related mitochondrial disease
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Май 14, 2024
Mitochondrial
diseases
(MtD)
represent
a
significant
public
health
challenge
due
to
their
heterogenous
clinical
presentation,
often
severe
and
progressive
symptoms,
the
lack
of
effective
therapies.
Environmental
exposures,
such
bacterial
viral
infection,
can
further
compromise
mitochondrial
function
exacerbate
progression
MtD.
Infections
in
MtD
patients
more
frequently
progress
sepsis,
pneumonia,
other
detrimental
inflammatory
endpoints.
However,
underlying
immune
alterations
that
enhance
immunopathology
remain
unclear,
constituting
key
gap
knowledge
complicates
treatment
increases
mortality
this
population.
Here
we
employ
vitro
vivo
approaches
clarify
molecular
cellular
basis
for
innate
hyperactivity
models
polymerase
gamma
(Polg)-related
We
reveal
type
I
interferon
(IFN-I)-mediated
upregulation
caspase-11
guanylate-binding
proteins
(GBPs)
increase
macrophage
sensing
opportunistic
microbe
Язык: Английский
STING exerts antiviral innate immune response by activating pentose phosphate pathway
Cell Communication and Signaling,
Год журнала:
2024,
Номер
22(1)
Опубликована: Дек. 18, 2024
The
innate
immune
system
serves
as
the
host's
first
line
of
defense
against
invading
pathogens.
Stimulator
interferon
genes
(STING)
is
a
key
component
this
system,
yet
its
relationship
with
glucose
metabolism,
particularly
in
antiviral
immunity,
remains
underexplored.
Metabolomics
analysis
was
used
for
detecting
metabolic
alterations
spleens
from
STING
knockout
(KO)
and
wild-type
(WT)
mice.
Co-immunoprecipitation
employed
determining
ubiquitination
TKT.
Mass
spectrometry
interaction
proteins
STING.
Enzyme
activity
kits
were
activities
TKT
G6PD.
In
study,
we
demonstrate
that
herpes
simplex
virus
(HSV)
infection
activates
pentose
phosphate
pathway
(PPP)
host
cells,
thereby
initiating
an
response.
Using
STING-manipulated
cells
systemic
mice,
show
positively
regulates
PPP,
which,
turn,
limits
HSV
infection.
Inhibition
PPP
significantly
reduced
production
factors
dampened
STING-induced
responses.
Mechanistically,
discovered
interacts
transketolase
(TKT),
enzyme
non-oxidative
branch
reduces
via
E3
ubiquitin
ligase
UBE3A,
stabilizing
Silencing
or
inhibiting
oxythiamine
diminished
factor
production.
Our
findings
reveal
plays
synergistic
role
generating
during
viral
suggest
activation
could
serve
adjunct
strategy
therapy.
Язык: Английский
Clinical features and treatment of stroke-like episodes in mitochondrial disease: a cohort-based study
Journal of Neurology,
Год журнала:
2024,
Номер
272(1)
Опубликована: Дек. 12, 2024
Abstract
Background
Stroke-like
episode
(SLE)
is
a
subacute
evolving
brain
syndrome
in
patients
with
primary
mitochondrial
diseases.
Despite
previous
research,
the
understanding
of
clinical
spectrum,
treatment,
and
outcomes
SLEs
far
from
complete.
In
this
single
centre
study,
we
report
symptoms
radiological
findings
as
well
medical
treatment
disease.
Methods
This
retrospective,
observational
study
during
years
2000–2023
was
based
on
cohort
diagnosed
disease
at
Turku
University
Hospital
(TUH;
Turku,
Finland)
region
Southwest
Finland.
Data
were
obtained
hospital
electronic
record
system.
Results
The
investigated
consisted
76
(37
men,
39
women)
diagnosis
Among
these,
12
had
history
least
one
SLE;
total
number
20.
most
common
genetic
aetiology
among
m.3243A
>
G
(N
=
7).
mean
age
first
SLE
40
(range:
5–66
years),
interval
between
episodes
4.8
4
months—10
years).
duration
varied
1
193
days
(median
14
days,
37
days);
10
needed
intensive
care
unit
(ICU)
treatment.
survival
time
death
3.6
0–16
Conclusion
Our
highlights
importance
early
recognition
prompt
management
symptoms,
especially
epileptic
seizures,
life-threatening
entity.
Язык: Английский