bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Aug. 20, 2024
Abstract
Neurodegenerative
disorders
alter
mitochondrial
functions,
including
the
production
of
reactive
oxygen
species
(ROS).
Mitochondrial
complex
III
(CIII)
generates
ROS
implicated
in
redox
signaling,
but
its
triggers,
targets,
and
disease
relevance
are
not
clear.
Using
site-selective
suppressors
genetic
manipulations
together
with
imaging
multiomic
profiling,
we
found
that
CIII
is
dominant
source
astrocytes
exposed
to
neuropathology-related
stimuli.
Astrocytic
CIII-ROS
was
dependent
on
nuclear
factor-κB
(NF-κB)
sodium-calcium
exchanger
(NCLX)
caused
oxidation
select
cysteines
within
immune
metabolism-associated
proteins
linked
neurological
disease.
amplified
metabolomic
pathology-associated
transcriptional
changes
astrocytes,
STAT3
activity
as
a
major
mediator,
facilitated
neuronal
toxicity
non-cell-
autonomous
manner.
As
proof-of-concept,
suppression
mice
decreased
dementia-linked
tauopathy
neuroimmune
cascades
extended
lifespan.
Our
findings
establish
an
important
immunometabolic
signal
transducer
tractable
therapeutic
target
neurodegenerative
Cancer Letters,
Journal Year:
2021,
Volume and Issue:
515, P. 28 - 35
Published: May 28, 2021
Many
organs
experience
a
loss
of
tissue
mass
and
decline
in
regenerative
capacity
during
aging.
In
contrast,
the
prostate
continues
to
grow
volume.
fact,
age
is
most
important
risk
factor
for
cancer.
However,
age-related
factors
that
influence
composition,
morphology
molecular
features
epithelial
progenitor
cells,
cells-of-origin
cancer,
are
poorly
understood.
Here,
we
review
evidence
luminal
cells
expanded
with
age.
We
explore
changes
microenvironment
may
transformation.
Finally,
raise
series
questions
about
models
aging
regulators
which
need
be
addressed.
A
fundamental
understanding
will
yield
critical
insights
into
mechanisms
promote
development
prostatic
disease.
Development,
Journal Year:
2023,
Volume and Issue:
150(20)
Published: Oct. 15, 2023
Metabolic
switches
are
a
crucial
hallmark
of
cellular
development
and
regeneration.
In
response
to
changes
in
their
environment
or
physiological
state,
cells
undergo
coordinated
metabolic
switching
that
is
necessary
execute
biosynthetic
demands
growth
repair.
this
Review,
we
discuss
how
represent
an
evolutionarily
conserved
mechanism
orchestrates
tissue
regeneration,
allowing
adapt
rapidly
changing
conditions
during
postnatally.
We
further
explore
the
dynamic
interplay
between
metabolism
it
not
only
output,
but
also
driver
functions,
such
as
cell
proliferation
maturation.
Finally,
underscore
epigenetic
mechanisms
by
which
mediate
needs
understanding
these
important
for
advancing
our
knowledge
devising
new
strategies
promote
Cells,
Journal Year:
2023,
Volume and Issue:
12(8), P. 1124 - 1124
Published: April 10, 2023
Reprogramming
energy
production
from
mitochondrial
respiration
to
glycolysis
is
now
considered
a
hallmark
of
cancer.
When
tumors
grow
beyond
certain
size
they
give
rise
changes
in
their
microenvironment
(e.g.,
hypoxia,
mechanical
stress)
that
are
conducive
the
upregulation
glycolysis.
Over
years,
however,
it
has
become
clear
can
also
associate
with
earliest
steps
tumorigenesis.
Thus,
many
oncoproteins
most
commonly
involved
tumor
initiation
and
progression
upregulate
Moreover,
recent
considerable
evidence
been
reported
suggesting
upregulated
itself,
through
its
enzymes
and/or
metabolites,
may
play
causative
role
tumorigenesis,
either
by
acting
itself
as
an
oncogenic
stimulus
or
facilitating
appearance
mutations.
In
fact,
several
induced
have
shown
be
early
tumorigenesis:
glycolysis-induced
chromatin
remodeling,
inhibition
premature
senescence
induction
proliferation,
effects
on
DNA
repair,
O-linked
N-acetylglucosamine
modification
target
proteins,
antiapoptotic
effects,
epithelial–mesenchymal
transition
autophagy,
angiogenesis.
this
article
we
summarize
and,
following,
propose
mechanistic
model
aimed
at
explaining
how
such
role.
Wound Repair and Regeneration,
Journal Year:
2022,
Volume and Issue:
31(2), P. 139 - 155
Published: Dec. 26, 2022
Our
previous
study
demonstrated
altered
glucose
metabolism
and
enhanced
phosphorylation
of
the
PI3K/AKT
pathway
in
keloid
fibroblasts
(KFb)
under
hypoxic
conditions.
However,
whether
influences
KFb
cell
function
by
regulating
conditions
remains
unclear.
Here,
we
show
that
when
was
inactivated
with
LY294002,
protein
expression
glycolytic
enzymes
decreased,
while
amount
mitochondria
mitochondrial
membrane
potential
increased.
The
key
parameters
extracellular
acidification
rate
markedly
diminished,
those
oxygen
consumption
significantly
increased
after
inhibition
pathway.
When
suppressed,
levels
reactive
species
(ROS)
ROS
(mitoROS)
were
Meanwhile,
proliferation,
migration
invasion
inhibited,
apoptosis
blocked.
Additionally,
proliferation
compromised
treated
both
SC79
(an
activator
pathway)
2-deoxy-d-glucose
inhibitor
glycolysis),
compared
group.
Moreover,
a
positive
feedback
mechanism
between
hypoxia-inducible
factor-1α
(HIF-1α).
data
collectively
promotes
inhibits
hypoxia
glycolysis,
indicating
signalling
could
be
therapeutic
target
for
keloids.
Annals of the New York Academy of Sciences,
Journal Year:
2025,
Volume and Issue:
unknown
Published: April 25, 2025
Abstract
The
intestines
play
important
roles
in
responding
immediately
and
dynamically
to
food
intake,
environmental
stress,
metabolic
dysfunction,
they
are
involved
various
human
diseases
aging.
A
key
part
of
their
function
is
governed
by
intestinal
stem
cells
(ISCs);
therefore,
understanding
ISCs
vital.
Dysregulation
ISC
activity,
which
influenced
cell
signaling
pathways
signals,
can
lead
inflammatory
responses,
tissue
damage,
increased
cancer
susceptibility.
Aging
exacerbates
these
dynamics
affects
elasticity.
Additionally,
proliferation
differentiation
profoundly
affect
behavior
gut
health,
highlighting
the
complex
interplay
between
factors
homeostasis.
Drosophila
models
help
us
understand
regulatory
networks
gut,
providing
valuable
insights
into
disease
mechanisms
therapeutic
strategies
targeting
diseases.
