International Journal of Molecular Medicine,
Год журнала:
2024,
Номер
55(3)
Опубликована: Дек. 31, 2024
Cardiovascular
disease
(CVD)
is
currently
a
major
factor
affecting
human
physical
and
mental
health.
In
recent
years,
the
relationship
between
intracellular
Ca2+
CVD
has
been
extensively
studied.
movement
across
mitochondrial
inner
membrane
plays
vital
role
as
an
messenger,
regulating
energy
metabolism
calcium
homeostasis.
It
also
involved
in
pathological
processes
such
cardiomyocyte
apoptosis,
hypertrophy
fibrosis
CVD.
The
selective
uniporter
complex
(MCU
complex)
located
essential
for
uptake.
Therefore,
MCU
potential
therapeutic
target
this
review,
research
progress
on
pathophysiological
mechanisms
of
various
CVDs
was
summarized,
including
myocardial
ischemia‑reperfusion
injury,
pulmonary
arterial
hypertension,
other
peripheral
vascular
diseases,
remodeling
arrhythmias.
This
review
contributes
to
deeper
understanding
these
at
molecular
level
highlights
intervention
targets
treatment
clinical
practice.
Endothelial
cells
(ECs)
are
highly
plastic,
capable
of
differentiating
into
various
cell
types.
Endothelial-to-mesenchymal
transition
(EndMT)
is
crucial
during
embryonic
development
and
contributes
substantially
to
vascular
dysfunction
in
many
cardiovascular
diseases
(CVDs).
While
targeting
EndMT
holds
therapeutic
promise,
understanding
its
mechanisms
modulating
pathways
remain
challenging.
Using
single-cell
RNA
sequencing
on
three
vitro
models,
we
identified
conserved
gene
signatures.
We
validated
original
regulators
vivo
heart
peripheral
artery
disease.
induction
led
global
expression
changes
all
EC
subtypes
rather
than
mesenchymal
clusters.
mitochondrial
calcium
uptake
as
a
key
driver
EndMT;
inhibiting
uniporter
(MCU)
prevented
vitro,
conditional
International Journal of Molecular Sciences,
Год журнала:
2025,
Номер
26(10), С. 4732 - 4732
Опубликована: Май 15, 2025
With
rapid
societal
changes
and
increasing
stress
levels,
the
abuse
of
psychoactive
substances
has
emerged
as
a
global
health
crisis.
Studies
indicate
that
mitochondrial
calcium
uniporter
(MCU)
plays
pivotal
role
in
neurotoxic
damage
induced
by
substances.
As
primary
channel
for
Ca2+
uptake,
MCU
dysfunction
can
lead
to
overload,
oxidative
stress,
apoptosis,
representing
crucial
mechanism
underlying
damage.
Psychoactive
such
3,4-Methylenedioxymethamphetamine
(MDMA),
cocaine,
morphine
influence
function
through
multiple
pathways,
resulting
excessive
accumulation
dysfunction,
ultimately
leading
neuronal
injury.
Although
inhibitors
have
demonstrated
potential
alleviating
overload
improving
neural
preliminary
studies,
their
selectivity
long-term
safety
require
further
evaluation.
Future
research
should
explore
precise
regulatory
mechanisms
develop
more
effective
targeted
therapeutic
strategies.
International Journal of Drug Discovery and Pharmacology,
Год журнала:
2024,
Номер
unknown, С. 100008 - 100008
Опубликована: Июнь 6, 2024
Review
Emerging
and
Novel
Therapeutic
Treatments
Targeting
Mitochondrial-Endoplasmic
Reticulum
Contact
Sites
in
Metabolic
Vascular
Disorders
Richard
M.
Monaghan
The
British
Heart
Foundation
Centre
of
Research
Excellence
Manchester,
Division
Cardiovascular
Sciences,
Faculty
Biology,
Medicine,
Health,
University
AV
Hill
Building,
Oxford
Road,
M13
9PN,
UK;[email protected]
Received:
10
April
2024;
Revised:
5
May
Accepted:
7
Published:
6
June
2024
Abstract:
Subcellular
organellar
contact
sites,
particularly
those
between
mitochondria
the
endoplasmic
reticulum
(MERCSs),
play
crucial
roles
maintaining
health.
These
specialized
partitions
facilitate
vital
communication
organelles,
regulating
processes
essential
for
cell
function,
including
calcium
balance,
lipid
biogenesis
transport,
mitochondrial
dynamics,
programmed
death.
Growing
evidence
shows
that
perturbation
MERCSs
contributes
significantly
to
various
diseases,
neurodegenerative
disorders
like
Alzheimer’s
Parkinson’s,
metabolic
issues,
such
as
type
2
diabetes,
heart
conditions,
cancer.
This
review
dives
into
this
expanding
field,
exploring
potential
therapeutic
targets.
It
provides
a
detailed
overview
proteins
form
maintain
MERCSs,
highlighting
how
their
disruption
can
lead
cellular
dysfunction
disease.
Additionally,
it
examines
recent
exciting
breakthroughs
developing
drugs
strategies
manipulate
clinical
benefits.
While
challenges
remain,
emphasises
MERCS-based
therapies
outlines
critical
research
needed
move
these
treatments
from
lab
clinic.
Biochemical Society Transactions,
Год журнала:
2024,
Номер
52(5), С. 2215 - 2229
Опубликована: Окт. 11, 2024
The
mitochondrial
intermembrane
space
(IMS)
is
a
highly
protected
compartment,
second
only
to
the
matrix.
It
crucial
bridge,
coordinating
activities
with
cellular
processes
such
as
metabolites,
protein,
lipid,
and
ion
exchange.
This
regulation
influences
signaling
pathways
for
metabolic
homeostasis.
IMS
harbors
various
proteins
critical
initiating
apoptotic
cascades
regulating
reactive
oxygen
species
production
by
controlling
respiratory
chain.
Calcium
(Ca2+),
key
intracellular
secondary
messenger,
enter
matrix
via
IMS,
bioenergetics,
ATP
production,
modulating
cell
death
pathways.
acts
regulatory
site
Ca2+
entry
due
presence
of
different
sensors
MICUs,
solute
carriers
(SLCs);
exchangers
(LETM1/SCaMCs);
S100A1,
glycerol-3-phosphate
dehydrogenase,
EFHD1,
each
unique
binding
motifs
spatial
localizations.
review
primarily
emphasizes
role
these
IMS-localized
concerning
their
localization,
mechanism,
molecular
functions.
Additionally,
we
discuss
how
contribute
progression
pathogenesis
human
health
conditions
diseases.
Journal of Cancer,
Год журнала:
2024,
Номер
15(12), С. 3663 - 3674
Опубликована: Янв. 1, 2024
In
this
study,
we
aimed
to
elucidate
the
role
of
mitochondrial
calcium
uptake
1/2
(MiCU1/2)
in
breast
cancer
(BRCA)
by
employing
a
comprehensive
multi-omics
approach.Unlike
previous
research,
utilized
novel
web
application
tailored
for
whole
tumor
tissue,
single-cell,
and
spatial
transcriptomics
analysis
investigate
association
between
MiCU1/2
immune
microenvironment
(TIME).Our
gene
set
enrichment
(GSEA)
provided
insights
into
primary
biological
effects
MiCU1/2,
while
our
CRISPR-based
drug
screening
repository
identified
potential
effective
drugs.Our
study
revealed
that
high
expression
serves
as
an
independent
diagnostic
biomarker,
correlating
with
advanced
clinical
status
indicating
poorer
recurrence-free
survival
(RFS)
rates
BRCA
patients.Additionally,
transcriptome
highlighted
heightened
tumors
its
relevance
surrounding
cells.Furthermore,
using
CIBERSORT
algorithm,
discovered
positive
correlation
levels
macrophage
infiltration,
underscoring
their
impact
on
infiltration.We
also
patterns
immune-related
genes
associated
responses
against
various
cell
types,
including
CXCL,
MIF,
GDF,
SPP1,
IL16.Finally,
pharmacogenomic
small
molecule
drugs
capable
effectively
targeting
cells
elevated
expression.Overall,
establishes
promising
biomarker
diagnosis
prognostic
prediction,
well
therapeutic
target,
highlighting
importance
exploring
these
pathways
advance
patient
care
outcomes
treatment.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Авг. 9, 2024
Abstract
Endoplasmic
reticulum
to
mitochondria
Ca
2+
transfer
is
important
for
cancer
cell
survival,
but
the
role
of
mitochondrial
uptake
through
uniporter
(MCU)
in
pancreatic
adenocarcinoma
(PDAC)
poorly
understood.
Here,
we
show
that
increased
MCU
expression
associated
with
malignancy
and
poorer
outcomes
PDAC
patients.
In
isogenic
murine
models,
Mcu
deletion
(
KO
)
ablated
uptake,
which
reduced
proliferation
inhibited
self-renewal.
Orthotopic
implantation
MCU-null
tumor
cells
primary
growth
metastasis.
cellular
plasticity
by
inhibiting
epithelial-to-mesenchymal
transition
(EMT),
contributes
metastatic
competency
PDAC.
Mechanistically,
loss
key
EMT
transcription
factor
Snail
secretion
EMT-inducing
ligand
TGFβ.
re-expression
TGFβ
treatment
rescued
deficits
restored
their
ability.
Thus,
may
present
a
therapeutic
target
limit
cancer-cell-induced
