Advanced Science,
Journal Year:
2024,
Volume and Issue:
unknown
Published: July 29, 2024
High-performance
biosensors
play
a
crucial
role
in
elucidating
the
intricate
spatiotemporal
regulatory
roles
and
dynamics
of
membrane
phospholipids.
However,
enhancing
sensitivity
imaging
performance
remains
significant
challenge.
Here,
optogenetic-based
strategies
are
presented
to
optimize
phospholipid
biosensors.
These
involves
presequestering
unbound
cell
nucleus
regulating
their
cytosolic
levels
with
blue
light
minimize
background
signal
interference
detection,
particularly
under
conditions
high
expression
biosensor.
Furthermore,
optically
controlled
phase
separation
SunTag
system
employed
generate
punctate
probes
for
substrate
thereby
amplifying
biosensor
signals
visualization
detection
process.
improved
hold
great
potential
understanding
lipids
live
cells
methodological
insights
this
study
might
be
valuable
developing
other
high-performance
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: April 13, 2024
Summary
Thioredoxin-related
transmembrane
proteins
(TMX)
of
the
endoplasmic
reticulum
(ER)
have
emerged
as
key
regulators
ER
membrane
properties.
Within
lumen,
TMX
and
other
redox
enzymes
determine
oxidative
conditions,
which
control
formation
ER-mitochondria
contacts
(ERMCS)
their
function.
ERMCS
exhibit
cytoplasmic
nanodomains,
derived
from
mitochondrial
reactive
oxygen
species
(ROS),
whose
mechanistic
regulation
is
uncharacterized.
Our
research
has
identified
protein
TMX2,
uses
its
unique
cytosolic
thioredoxin
domain
to
prevent
sulfenylation
outer
such
TOM70
through
a
functional
interaction
with
peroxiredoxin-1
(PRDX1).
By
doing
so,
TMX2
interferes
tethering
function
reduces
Ca
2+
flux
metabolism.
Recently,
mutations
been
cause
neurodevelopmental
disorder
microcephaly,
cortical
malformations,
spasticity
(NEDMCMS).
Using
TMX2-mutated
NEDMCMS
patient
cells,
we
demonstrate
that
compromising
mutation
reproduces
defects.
In
fly
in
vivo
model,
knockdown
manifests
predominantly
glial
cells.
results
therefore
provide
important
insight
into
mechanistically
link
TMX2-mediated
brain
development
Graphical
Abstract
The
thioredoxin-related
prevents
at
ERMCS,
thus
maintaining
normal
mitochondria
metabolism
wild-type
knockout
leads
tight
formation.
This
then
increases
ROS
production,
unbalances
lipids,
relatively
shifts
OXPHOS
electron
supply
complex
II.
Frontiers in Cell and Developmental Biology,
Journal Year:
2023,
Volume and Issue:
11
Published: Dec. 7, 2023
The
Integrated
Stress
Response
(ISR)
is
an
essential
homeostatic
signaling
network
that
controls
the
cell's
biosynthetic
capacity.
Four
ISR
sensor
kinases
detect
multiple
stressors
and
relay
this
information
to
downstream
effectors
by
phosphorylating
a
common
node:
alpha
subunit
of
eukaryotic
initiation
factor
eIF2.
As
result,
general
protein
synthesis
repressed
while
select
transcripts
are
preferentially
translated,
thus
remodeling
proteome
transcriptome.
Mounting
evidence
supports
view
as
dynamic
with
modulators
feedback
regulatory
features
vary
across
cell
tissue
types.
Here,
we
discuss
updated
views
on
kinase
mechanisms,
how
subcellular
localization
components
impacts
signaling,
highlight
differences
cells
tissues.
Finally,
consider
crosstalk
between
other
pathways
determinant
health.
Canadian Journal of Physiology and Pharmacology,
Journal Year:
2024,
Volume and Issue:
unknown
Published: July 5, 2024
Lysophosphatidic
acid
(LPA)
is
a
bioactive
lipid
that
mainly
produced
by
the
secreted
lysophospholipase
D,
autotaxin
(ATX),
and
signals
through
at
least
six
G
protein-coupled
receptors
(LPA1-6).
Extracellular
LPA
degraded
phosphate
phosphatases
(LPP1,
LPP2,
LPP3)
plasmamembrane,
terminating
receptor
signaling.
The
ATX-LPA-LPP3
pathway
critically
involved
in
wide
range
of
physiological
processes,
including
cell
survival,
migration,
proliferation,
angiogenesis,
organismal
development.
Similarly,
dysregulation
this
has
been
linked
to
many
pathological
cardiovascular
disease.
This
review
summarizes
interprets
current
literature
examining
regulation
role
axis
heart
Specifically,
contribution
altered
metabolism
via
ATX
LPP3
resulting
changes
signaling
obesity
cardiomyopathy,
cardiac
mitochondrial
dysfunction,
myocardial
infarction/ischemia-reperfusion
injury,
hypertrophic
aortic
valve
stenosis
discussed.
Advanced Science,
Journal Year:
2024,
Volume and Issue:
unknown
Published: July 29, 2024
High-performance
biosensors
play
a
crucial
role
in
elucidating
the
intricate
spatiotemporal
regulatory
roles
and
dynamics
of
membrane
phospholipids.
However,
enhancing
sensitivity
imaging
performance
remains
significant
challenge.
Here,
optogenetic-based
strategies
are
presented
to
optimize
phospholipid
biosensors.
These
involves
presequestering
unbound
cell
nucleus
regulating
their
cytosolic
levels
with
blue
light
minimize
background
signal
interference
detection,
particularly
under
conditions
high
expression
biosensor.
Furthermore,
optically
controlled
phase
separation
SunTag
system
employed
generate
punctate
probes
for
substrate
thereby
amplifying
biosensor
signals
visualization
detection
process.
improved
hold
great
potential
understanding
lipids
live
cells
methodological
insights
this
study
might
be
valuable
developing
other
high-performance
