Journal of Hepatology,
Год журнала:
2022,
Номер
77(3), С. 710 - 722
Опубликована: Март 28, 2022
Hepatic
insulin
resistance
in
obesity
and
type
2
diabetes
was
recently
associated
with
endoplasmic
reticulum
(ER)-mitochondria
miscommunication.
These
contact
sites
(mitochondria-associated
membranes:
MAMs)
are
highly
dynamic
involved
many
functions;
however,
whether
MAM
dysfunction
plays
a
causal
role
hepatic
steatosis
is
not
clear.
Thus,
we
aimed
to
determine
how
organelle
miscommunication
the
onset
progression
of
metabolic
impairment.We
analyzed
ER-mitochondria
interactions
calcium
exchange
time-dependent
reversible
manner
mice
diet-induced
obesity.
Additionally,
used
recombinant
adenovirus
express
specific
spacer
or
linker
mouse
livers,
impact
on
alterations.Disruption
an
early
event
preceding
Interestingly,
8-week
reversal
diet
concomitantly
reversed
obese
mice.
Mechanistically,
disrupting
structural
functional
through
overexpression
FATE1
sufficient
impair
action
glucose
homeostasis.
In
addition,
FATE1-mediated
disrupted
lipid-related
mitochondrial
oxidative
metabolism
induced
steatosis.
Conversely,
reinforcement
expression
synthetic
prevented
intolerance
after
4
weeks'
overnutrition.
Importantly,
confirmed
liver
patients
diabetes,
correlated
glycemia,
HbA1c
HOMA-IR
index.ER-mitochondria
trigger
steatosis,
can
be
by
switching
healthy
diet.
targeting
MAMs
could
help
restore
homeostasis.The
literature
suggests
that
between
mitochondria
play
during
chronic
present
study,
reappraised
regulation
reticulum-mitochondria
exchange,
investigating
reversibility
causality,
We
also
assessed
relevance
our
findings
humans.
show
improved
nutritional
strategies.
Signal Transduction and Targeted Therapy,
Год журнала:
2023,
Номер
8(1)
Опубликована: Сен. 15, 2023
Abstract
The
endoplasmic
reticulum
(ER)
functions
as
a
quality-control
organelle
for
protein
homeostasis,
or
“proteostasis”.
quality
control
systems
involve
ER-associated
degradation,
chaperons,
and
autophagy.
ER
stress
is
activated
when
proteostasis
broken
with
an
accumulation
of
misfolded
unfolded
proteins
in
the
ER.
activates
adaptive
response
to
restore
by
initiating
kinase
R-like
kinase,
activating
transcription
factor
6,
inositol
requiring
enzyme
1.
multifaceted,
acts
on
aspects
at
epigenetic
level,
including
processing.
Accumulated
data
indicates
its
key
role
homeostasis
other
diverse
involved
various
ocular
diseases,
such
glaucoma,
diabetic
retinopathy,
age-related
macular
degeneration,
retinitis
pigmentosa,
achromatopsia,
cataracts,
tumors,
surface
myopia.
This
review
summarizes
molecular
mechanisms
underlying
aforementioned
diseases
from
perspective.
Drugs
(chemicals,
neurotrophic
factors,
nanoparticles),
gene
therapy,
stem
cell
therapy
are
used
treat
alleviating
stress.
We
delineate
advancement
targeting
provide
new
treatment
strategies
diseases.
The
cytosol-facing
membranes
of
cellular
organelles
contain
proteins
that
enable
signal
transduction,
regulation
morphology
and
trafficking,
protein
import
export,
other
specialized
processes.
Discovery
these
by
traditional
biochemical
fractionation
can
be
plagued
with
contaminants
loss
key
components.
Using
peroxidase-mediated
proximity
biotinylation,
we
captured
identified
endogenous
on
the
outer
mitochondrial
membrane
(OMM)
endoplasmic
reticulum
(ERM)
living
human
fibroblasts.
proteomes
137
634
proteins,
respectively,
are
highly
specific
highlight
94
potentially
novel
or
ER
proteins.
Dataset
intersection
candidates
localized
to
mitochondria-ER
contact
sites.
We
found
one
candidate,
tail-anchored,
PDZ-domain-containing
OMM
SYNJ2BP,
dramatically
increases
contacts
rough
when
overexpressed.
Immunoprecipitation-mass
spectrometry
ribosome-binding
1
(RRBP1)
as
SYNJ2BP's
ERM
binding
partner.
Our
results
power
biotinylation
yield
insights
into
molecular
composition
function
intracellular
membranes.
Nature Communications,
Год журнала:
2019,
Номер
10(1)
Опубликована: Авг. 19, 2019
Contact
sites
of
endoplasmic
reticulum
(ER)
and
mitochondria
locally
convey
calcium
signals
between
the
IP3
receptors
(IP3R)
mitochondrial
uniporter,
are
central
to
cell
survival.
It
remains
unclear
whether
IP3Rs
also
have
a
structural
role
in
contact
formation
different
IP3R
isoforms
redundant
functions.
Using
an
IP3R-deficient
model
rescued
with
each
three
array
super-resolution
ultrastructural
approaches
we
demonstrate
that
required
for
maintaining
ER-mitochondrial
contacts.
This
is
independent
fluxes.
We
show
that,
while
isoform
can
support
contacts,
type
2
most
effective
delivering
mitochondria.
Thus,
these
studies
reveal
non-canonical,
direct
attention
towards
was
previously
neglected
context
signaling.
