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
Frontiers in Neuroscience,
Journal Year:
2021,
Volume and Issue:
15
Published: Nov. 24, 2021
Frontotemporal
dementia
(FTD)
and
amyotrophic
lateral
sclerosis
(ALS)
are
neurodegenerative
disorders
characterized
by
declining
motor
cognitive
functions.
Even
though
these
diseases
present
with
distinct
sets
of
symptoms,
FTD
ALS
two
extremes
the
same
disease
spectrum,
as
they
show
considerable
overlap
in
genetic,
clinical
neuropathological
features.
Among
overlapping
features,
mitochondrial
dysfunction
is
associated
both
ALS.
Recent
studies
have
shown
that
cells
derived
from
patients’
induced
pluripotent
stem
(iPSC)s
display
abnormalities,
similar
abnormalities
been
observed
a
number
animal
models.
Drosophila
models
widely
used
to
study
because
their
rapid
generation
time
extensive
set
genetic
tools.
A
wide
array
fly
developed
elucidate
molecular
mechanisms
toxicity
for
mutations
FTD/ALS.
Fly
often
instrumental
understanding
role
mitochondria
biology.
In
this
review,
we
discuss
how
FTD/ALS
disrupt
function,
review
use
has
pivotal
our
current
knowledge
field.
Cell Regeneration,
Journal Year:
2022,
Volume and Issue:
11(1)
Published: Feb. 1, 2022
Cell
metabolism
plays
vital
roles
in
organismal
development,
but
it
has
been
much
less
studied
than
transcriptional
and
epigenetic
control
of
developmental
programs.
The
difficulty
might
be
largely
attributed
to
the
lack
situ
metabolite
assays.
Genetically
encoded
fluorescent
sensors
are
powerful
tools
for
noninvasive
metabolic
monitoring
living
cells
vivo
by
highly
spatiotemporal
visualization.
Among
all
organisms,
NAD(H)
NADP(H)
pools
essential
maintaining
redox
homeostasis
modulating
cellular
metabolism.
Here,
we
introduce
biosensors,
present
example
assays
developing
describe
promising
prospects
how
contribute
biology
research.
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.
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
