Oxidative Medicine and Cellular Longevity,
Год журнала:
2021,
Номер
2021(1)
Опубликована: Янв. 1, 2021
The
normal
function
of
the
mitochondria
is
crucial
for
most
tissues
especially
those
that
demand
a
high
energy
supply.
Emerging
evidence
has
pointed
out
healthy
mitochondrial
closely
associated
with
heart
function.
When
these
processes
fail
to
repair
damaged
mitochondria,
cells
initiate
removal
process
referred
as
mitophagy
clear
away
defective
mitochondria.
In
cardiomyocytes,
metabolic
activity,
cell
differentiation,
apoptosis,
and
other
physiological
involved
in
major
phenotypic
alterations.
Mitophagy
alterations
may
contribute
detrimental
or
beneficial
effects
multitude
cardiac
diseases,
indicating
potential
clinical
insights
after
close
understanding
mechanisms.
Here,
we
discuss
current
opinions
progression
such
ischemic
disease,
diabetic
cardiomyopathy,
hypertrophy,
failure,
arrhythmia,
focus
on
key
molecules
related
pathways
regulation
mitophagy.
We
also
recently
reported
approaches
targeting
therapy
diseases.
International Journal of Biological Sciences,
Год журнала:
2022,
Номер
19(2), С. 426 - 448
Опубликована: Дек. 19, 2022
Ischemic
cardiomyopathy
(ICM)
is
a
special
type
of
coronary
heart
disease
or
an
advanced
stage
the
disease,
which
related
to
pathological
mechanism
primary
dilated
cardiomyopathy.
mainly
occurs
in
long-term
myocardial
ischemia,
resulting
diffuse
fibrosis.
This
turn
affects
cardiac
ejection
function,
significant
impact
on
systolic
and
diastolic
decrease
fraction.
The
pathogenesis
ICM
closely
disease.
Mainly
due
atherosclerosis
caused
by
stenosis
vascular
occlusion,
causing
inflammatory
lesions
thrombosis.
As
progresses,
it
leads
ischemia
eventually
ICM.
mechanisms
inflammation,
hypertrophy,
fibrosis
remodeling.
Mitochondria
are
organelles
with
double-membrane
structure,
so
composition
mitochondrial
outer
compartment
basically
similar
that
cytoplasm.
When
ischemia-reperfusion
induces
large
influx
calcium
into
cell,
concentration
ions
also
increases.
subsequent
opening
membrane
permeability
transition
pore
inner
overload
homeostasis
cardiomyocytes
activates
pathway
apoptosis.
Mitochondrial
Quality
Control
(MQC),
as
important
for
regulating
function
cardiomyocytes,
morphological
structure/function
lifespan
mitochondria.
In
this
review,
we
discuss
role
MQC
(including
mitophagy,
dynamics,
biosynthesis)
provide
evidence
targeting
Inflammasome
activation
and
pyroptotic
cell
death
are
known
to
contribute
the
pathogenesis
of
cardiovascular
diseases,
such
as
myocardial
ischemia-reperfusion
(I/R)
injury,
although
underlying
regulatory
mechanisms
remain
poorly
understood.
Here
we
report
that
expression
levels
E3
ubiquitin
ligase
membrane-associated
RING
finger
protein
2
(MARCH2)
were
elevated
in
ischemic
human
hearts
or
mouse
upon
I/R
injury.
Genetic
ablation
MARCH2
aggravated
infarction
cardiac
dysfunction
Single-cell
RNA-seq
analysis
suggested
loss
prompted
NLRP3
inflammasome
cardiomyocytes.
Mechanistically,
phosphoglycerate
mutase
5
(PGAM5)
was
found
act
a
novel
regulator
MAVS-NLRP3
signaling
by
forming
liquid-liquid
phase
separation
condensates
with
MAVS
fostering
recruitment
NLRP3.
directly
interacts
PGAM5
promote
its
K48-linked
polyubiquitination
proteasomal
degradation,
resulting
reduced
PGAM5-MAVS
co-condensation,
consequently
inhibition
cardiomyocyte
pyroptosis.
AAV-based
re-introduction
significantly
ameliorated
I/R-induced
heart
dysfunction.
Altogether,
our
findings
reveal
mechanism
where
MARCH2-mediated
ubiquitination
negatively
regulates
PGAM5/MAVS/NLRP3
axis
protect
against
pyroptosis
Military Medical Research,
Год журнала:
2024,
Номер
11(1)
Опубликована: Май 29, 2024
Abstract
Mitochondria,
the
most
crucial
energy-generating
organelles
in
eukaryotic
cells,
play
a
pivotal
role
regulating
energy
metabolism.
However,
their
significance
extends
beyond
this,
as
they
are
also
indispensable
vital
life
processes
such
cell
proliferation,
differentiation,
immune
responses,
and
redox
balance.
In
response
to
various
physiological
signals
or
external
stimuli,
sophisticated
mitochondrial
quality
control
(MQC)
mechanism
has
evolved,
encompassing
key
like
biogenesis,
dynamics,
mitophagy,
which
have
garnered
increasing
attention
from
researchers
unveil
specific
molecular
mechanisms.
this
review,
we
present
comprehensive
summary
of
primary
mechanisms
functions
regulators
involved
major
components
MQC.
Furthermore,
critical
regulated
by
MQC
its
diverse
roles
progression
systemic
diseases
been
described
detail.
We
discuss
agonists
antagonists
targeting
MQC,
aiming
explore
potential
therapeutic
research
prospects
enhancing
stabilize
function.
Circulation Research,
Год журнала:
2024,
Номер
135(2), С. 372 - 396
Опубликована: Июль 4, 2024
Despite
clinical
and
scientific
advancements,
heart
failure
is
the
major
cause
of
morbidity
mortality
worldwide.
Both
mitochondrial
dysfunction
inflammation
contribute
to
development
progression
failure.
Although
crucial
reparative
healing
following
acute
cardiomyocyte
injury,
chronic
damages
heart,
impairs
function,
decreases
cardiac
output.
Mitochondria,
which
comprise
one
third
volume,
may
prove
a
potential
therapeutic
target
for
Known
primarily
energy
production,
mitochondria
are
also
involved
in
other
processes
including
calcium
homeostasis
regulation
cellular
apoptosis.
Mitochondrial
function
closely
related
morphology,
alters
through
dynamics,
thus
ensuring
that
needs
cell
met.
However,
failure,
changes
substrate
use
lead
impaired
myocyte
function.
This
review
discusses
cristae
role
contact
site
organizing
system
complex
ultrastructure
changes.
Additionally,
this
covers
mitochondria-endoplasmic
reticulum
sites,
communication
via
nanotunnels,
altered
metabolite
production
during
We
highlight
these
often-neglected
factors
promising
targets
Pharmacological Research,
Год журнала:
2024,
Номер
206, С. 107258 - 107258
Опубликована: Июнь 21, 2024
Several
cardiovascular
illnesses
are
associated
with
aberrant
activation
of
cellular
pyroptosis,
ferroptosis,
necroptosis,
cuproptosis,
disulfidptosis
and
macrophage
polarisation
as
hallmarks
contributing
to
vascular
damage
abnormal
cardiac
function.
Meanwhile,
these
three
novel
forms
dysfunction
closely
related
mitochondrial
homeostasis.
Mitochondria
the
main
organelles
that
supply
energy
maintain
Mitochondrial
stability
is
maintained
through
a
series
regulatory
pathways,
such
fission,
fusion
mitophagy.
Studies
have
shown
(e.g.,
impaired
dynamics
mitophagy)
promotes
ROS
production,
leading
oxidative
stress,
which
induces
M1
phenotypic
polarisation.
Therefore,
an
in-depth
knowledge
dynamic
regulation
mitochondria
during
necessary
understand
disease
development.
This
paper
systematically
summarises
impact
changes
in
mitophagy
on
regulating
dysfunctions
promote
understanding
pathogenesis
diseases
provide
corresponding
theoretical
references
for
treating
diseases.
