medRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2023,
Volume and Issue:
unknown
Published: Oct. 22, 2023
Abstract
Background
After
myocardial
infarction
(MI),
there
is
a
notable
disruption
in
cellular
calcium
ion
homeostasis
and
mitochondrial
function.
These
alterations
are
believed
to
be
linked
endoplasmic
reticulum
(ER)
stress,
though
the
specific
mechanisms
not
fully
understood.
This
research
endeavors
elucidate
involvement
of
glucose
regulated
protein
75
(GRP75)
post-MI
Results
Excessive
oxidative
stress
was
activated
humans’
post-myocardial
infarction,
with
most
differentially
expressed
genes
being
enriched
metabolic
pathways,
especially
signaling
pathway.
In
MI
rats,
symptoms
injury
were
accompanied
by
an
increase
activation
PERK,
ATF6,
IRE1,
as
well
elevated
Binding
immunoglobulin
(Bip)
expression.
Moreover,
oxygen-glucose
deprivation
(OGD)-induced
cardiomyocytes,
it
confirmed
that
inhibiting
PERK
exacerbated
intracellular
Ca
2+
cell
apoptosis.
More
importantly,
cardiomyocytes
undergoing
Tunicamycin-induced
ER
accumulated
both
mitochondria.
Concurrently,
co-localization
GRP75
IP3R
VDAC1
increased
under
cardiomyocytes.
OGD-induced
knockdown
only
reduced
levels
mitochondria
improved
ultrastructure
but
also
number
contact
points
between
mitochondria,
reducing
MAM
formation,
decreased
Significantly,
did
affect
expression
hypoxia-inducible
factor
1α
(HIF-1α).
Transcriptome
analysis
revealed
mainly
influenced
molecular
functions
sialyltransferase
IP3R,
biosynthesis
glycosphingolipids
lactate
metabolism.
lowered
transporter-1
(Glut1),
pyruvate
kinase
M2
(PKM2),
dehydrogenase
A
(LDHA),
products
glycolysis.
Conclusion
The
complex
interaction
driven
its
associated
IP3R1-GRP75-VDAC1
complex,
crucial
for
cardiomyocyte’s
adaptive
response
stress.
Modulating
could
offer
strategy
regulate
dynamics,
diminish
glycolysis,
thereby
mitigate
cardiomyocyte
Nature Communications,
Journal Year:
2023,
Volume and Issue:
14(1)
Published: Sept. 2, 2023
MAVS
is
an
adapter
protein
involved
in
RIG-I-like
receptor
(RLR)
signaling
mitochondria,
peroxisomes,
and
mitochondria-associated
ER
membranes
(MAMs).
However,
the
role
of
glucose
metabolism
RLR
cross-regulation
how
these
pathways
are
coordinated
among
organelles
have
not
been
defined.
This
study
reports
that
action
drives
a
switch
from
glycolysis
to
pentose
phosphate
pathway
(PPP)
hexosamine
biosynthesis
(HBP)
through
MAVS.
We
show
peroxisomal
responsible
for
flux
shift
into
PPP
type
III
interferon
(IFN)
expression,
whereas
MAMs-located
HBP
I
IFN
expression.
Mechanistically,
interacts
with
G6PD
signalosome
forms
at
peroxisomes
by
recruiting
TNF
receptor-associated
factor
6
(TRAF6)
regulatory
1
(IRF1).
By
contrast,
interact
glutamine-fructose-6-phosphate
transaminase,
MAMs
TRAF6
TRAF2.
Our
findings
suggest
mediates
interaction
metabolism.
Experimental & Molecular Medicine,
Journal Year:
2024,
Volume and Issue:
56(1), P. 40 - 50
Published: Jan. 4, 2024
Abstract
Dynamic
interactions
between
organelles
are
responsible
for
a
variety
of
intercellular
functions,
and
the
endoplasmic
reticulum
(ER)–mitochondrial
axis
is
recognized
as
representative
interorganelle
system.
Several
studies
have
confirmed
that
most
proteins
in
physically
tethered
sites
ER
mitochondria,
called
mitochondria-associated
membranes
(MAMs),
vital
intracellular
physiology.
MAM
involved
regulation
calcium
homeostasis,
lipid
metabolism,
mitochondrial
dynamics
associated
with
processes
related
to
stress
conditions,
such
oxidative
unfolded
protein
responses.
Accumulating
evidence
has
shown
that,
owing
their
extensive
involvement
cellular
alterations
ER–mitochondrial
one
etiological
factors
tumors.
An
in-depth
understanding
impact
on
cell
physiology,
particularly
cancers,
may
help
elucidate
potential
diagnostic
therapeutic
targets
cancers.
For
example,
modulation
utilized
not
only
target
diverse
signaling
pathways
within
cancer
cells
but
also
increase
sensitivity
anticancer
reagents
regulate
immune
activities.
Therefore,
current
review
summarizes
discusses
recent
advances
research
functional
roles
characteristics
cancers
from
perspective.
Additionally,
this
provides
insights
into
strategies
various
types.
International Journal of Molecular Sciences,
Journal Year:
2025,
Volume and Issue:
26(3), P. 894 - 894
Published: Jan. 22, 2025
Fuchs
endothelial
corneal
dystrophy
(FECD)
is
a
progressive
and
debilitating
disorder
of
the
endothelium
(CE)
that
affects
approximately
4%
individuals
over
age
40.
Despite
burden
disease,
pathogenesis
FECD
remains
poorly
understood,
treatment
options
are
limited,
highlighting
need
for
deeper
investigation
into
its
underlying
molecular
mechanisms.
Over
past
decade,
studies
have
indicated
independent
contributions
endoplasmic
reticulum
(ER)
mitochondrial
stress
to
FECD.
However,
there
limited
suggesting
ER-mitochondria
crosstalk
in
Recently,
our
lab
established
role
chronic
ER
inducing
dysfunction
cells
(CEnCs),
indicating
existence
This
paper
aims
provide
comprehensive
overview
current
understanding
how
contribute
pathogenesis.
The
also
reviews
literature
on
mechanisms
other
diseases
relevant
Ageing Research Reviews,
Journal Year:
2024,
Volume and Issue:
98, P. 102320 - 102320
Published: May 6, 2024
Aging
is
a
gradual
and
irreversible
natural
process.
With
aging,
the
body
experiences
functional
decline,
effects
amplify
vulnerability
to
range
of
age-related
diseases,
including
neurodegenerative,
cardiovascular,
metabolic
diseases.
Within
aging
process,
morphology
function
mitochondria
endoplasmic
reticulum
(ER)
undergo
alterations,
particularly
in
structure
connecting
these
organelles
known
as
mitochondria-associated
membranes
(MAMs).
MAMs
serve
vital
intracellular
signaling
hubs,
facilitating
communication
between
ER
when
regulating
various
cellular
events,
calcium
homeostasis,
lipid
metabolism,
mitochondrial
function,
apoptosis.
The
formation
partly
dependent
on
interaction
vesicle-associated
membrane
protein-associated
protein-B
(VAPB)
protein
tyrosine
phosphatase-interacting
protein-51
(PTPIP51).
Accumulating
evidence
has
begun
elucidate
pivotal
role
VAPB-PTPIP51
tether
initiation
progression
In
this
study,
we
delineate
intricate
multifunctional
discuss
its
profound
implications
aging-associated
Moreover,
provide
comprehensive
overview
potential
therapeutic
interventions
pharmacological
agents
targeting
VAPB-PTPIP51-mediated
MAMs,
thereby
offering
glimmer
hope
mitigating
processes
treating
disorders.
European Journal of Pharmacology,
Journal Year:
2024,
Volume and Issue:
971, P. 176530 - 176530
Published: March 24, 2024
After
myocardial
infarction
(MI),
there
is
a
notable
disruption
in
cellular
calcium
ion
homeostasis
and
mitochondrial
function,
which
believed
to
be
intricately
linked
endoplasmic
reticulum
(ER)
stress.
This
research
endeavors
elucidate
the
involvement
of
glucose
regulated
protein
75
(GRP75)
post-MI
function.
In
MI
rats,
symptoms
injury
were
accompanied
by
an
increase
activation
ER
Moreover,
oxygen-glucose
deprivation
(OGD)-induced
cardiomyocytes,
it
was
confirmed
that
inhibiting
stress
exacerbated
intracellular
Ca2+
cell
apoptosis.
Concurrently,
co-localization
GRP75
with
IP3R
VDAC1
increased
under
cardiomyocytes.
OGD-induced
knockdown
not
only
reduced
levels
both
mitochondria
improved
ultrastructure
but
also
number
contact
points
between
mitochondria,
reducing
associated
membrane
(MAM)
formation,
decreased
Significantly,
did
affect
expression
PERK
hypoxia-inducible
factor
1α
(HIF-1α).
Transcriptome
analysis
cardiomyocytes
revealed
mainly
influenced
molecular
functions
sialyltransferase
IP3R,
as
well
biosynthesis
glycosphingolipids
lactate
metabolism.
The
complex
interaction
driven
its
IP3R1-GRP75-VDAC1
complex,
crucial
for
cardiomyocyte's
adaptive
response
Modulating
could
offer
strategy
regulate
dynamics,
diminish
glycolysis,
thereby
mitigate
cardiomyocyte
Frontiers in Pharmacology,
Journal Year:
2024,
Volume and Issue:
15
Published: April 17, 2024
Cardiovascular
diseases
(CVDs)
are
currently
the
leading
cause
of
death
worldwide.
In
2022,
CVDs
contributed
to
19.8
million
deaths
globally,
accounting
for
one-third
all
global
deaths.
With
an
aging
population
and
changing
lifestyles,
pose
a
major
threat
human
health.
Mitochondria-associated
endoplasmic
reticulum
membranes
(MAMs)
communication
platforms
between
cellular
organelles
regulate
physiological
functions,
including
apoptosis,
autophagy,
programmed
necrosis.
Further
research
has
shown
that
MAMs
play
critical
role
in
pathogenesis
CVDs,
myocardial
ischemia
reperfusion
injury,
heart
failure,
pulmonary
hypertension,
coronary
atherosclerosis.
This
suggests
could
be
important
therapeutic
target
managing
CVDs.
The
goal
this
study
is
summarize
protein
complex
MAMs,
discuss
its
pathological
mechanisms
terms
functions
such
as
Ca
Journal of Translational Medicine,
Journal Year:
2024,
Volume and Issue:
22(1)
Published: June 9, 2024
Abstract
Acute
myocardial
infarction
(AMI)
is
a
serious
condition
that
occurs
when
part
of
the
heart
subjected
to
ischemia
episodes,
following
partial
or
complete
occlusion
epicardial
coronary
arteries.
The
resulting
damage
muscle
cells
have
significant
impact
on
patient’s
health
and
quality
life.
About
that,
recent
research
focused
role
sarcoplasmic
reticulum
(SR)
mitochondria
in
physiopathology
AMI.
Moreover,
SR
get
touch
each
other
through
multiple
membrane
contact
sites
giving
rise
subcellular
region
called
mitochondria-associated
membranes
(MAMs).
MAMs
are
essential
for,
but
not
limited
to,
bioenergetics
cell
fate.
Disruption
architecture
these
regions
during
AMI
although
it
still
unclear
cause-consequence
connection
overview
pathological
changes;
for
sure
this
concurs
further
muscle.
calcium
ion
(Ca
2+
)
plays
pivotal
pathophysiology
its
dynamic
signaling
between
holds
importance.
In
review,
we
tried
summarize
update
knowledge
about
roles
organelles
from
Ca
point
view.
Accordingly,
also
reported
some
possible
cardioprotective
targets
which
directly
indirectly
related
at
limiting
dysfunctions
caused
by
deregulation
signaling.
