Phospholipids
are
critical
building
blocks
of
mitochondria,
and
mitochondrial
proper
functions
architecture
rely
on
its
phospholipids
majorly
transported
from
the
endoplasmic
reticulum
(ER).
Here,
we
show
that
among
major
phospholipids,
trafficking
phosphatidylserine
(PS)
ER
to
mitochondria
converting
PS
phosphatidylethanolamine
(PE)
in
inner
membrane
(IMM)
for
maintaining
morphology
function.
Using
a
forward
genetic
screen
Drosophila,
found
Slowmo
(SLMO)
specifically
transfer
outer
(OMM)
IMM
within
boundary
(IBM)
domain,
is
required
shaping
morphology.
In
slmo
mutants,
flux
disrupted,
leading
fragmentation,
loss
cristae,
reduced
function,
locomotion
phenotypes,
neurodegeneration.
Importantly,
role
SLMO
plays
conserved
humans
via
SLMO2
protein
independent
dynamics.
Our
results
highlight
importance
PSS-SLMO-PISD
pathway
structure
function
mitochondria.
The Lancet Healthy Longevity,
Journal Year:
2024,
Volume and Issue:
5(7), P. e454 - e463
Published: June 27, 2024
BackgroundAgeing
hallmarks,
characterising
features
of
cellular
ageing,
have
a
role
in
the
pathophysiology
many
age-related
diseases.
We
examined
whether
obesity
is
associated
with
an
increased
risk
developing
such
hallmark-related
diseases.MethodsIn
this
multicohort
study,
we
included
people
aged
38–72
years
data
on
weight,
height,
and
waist
circumference
measured
during
clinical
examination
at
baseline
between
March
13,
2006,
Oct
1,
2010,
from
UK
Biobank
follow-up
until
Nov
12,
2021.
To
test
reproducibility
findings
(replication
analysis),
used
40
or
older
Finnish
Public
Sector
study
Health
Social
Support
who
responded
to
surveys,
had
BMI,
were
successfully
linked
electronic
health
records
national
registers
up
Dec
31,
2016.
Obesity
characteristics
assessed
baseline.
Via
linkage
records,
participants
followed
for
83
diseases
related
nine
ageing
hallmarks
(genomic
instability,
telomere
attrition,
epigenetic
alterations,
loss
proteostasis,
deregulated
nutrient
sensing,
mitochondrial
dysfunction,
senescence,
stem
cell
exhaustion,
altered
intercellular
communication).
Outcomes
first
instance
disease,
addition
co-occurrence
three
more
mortality.Findings496
530
adults
(mean
age
57·0
[SD
8·1])
primary
analysis,
249
48·2
[6·4])
cohorts
replication
analysis.
Median
was
12·7
(IQR
12·0–13·4)
14·0
(8·0–15·0)
cohorts.
After
adjusting
demographic
characteristics,
lifestyle
factors,
depression,
(BMI
≥30·0
kg/m2)
1·40
(95%
CI
1·38–1·41)
times
higher
hazard
ratio
disease
than
those
healthy
weight
18·5–24·9
kg/m2).
The
corresponding
ratios
co-occurring
2·92
2·64–3·22)
2·73
(2·46–3·02)
2·33
(2·10–2·60)
2·30
(2·14–2·48)
2·23
(2·04–2·45)
2·02
(1·89–2·16)
communication,
2·01
(1·89–2·15)
1·83
(1·67–2·00)
1·39
(1·27–1·52)
genomic
instability.
These
replicated
In
both
studies,
associations
other
factors
(low
education,
unhealthy
dietary
[available
only
Biobank],
smoking,
high
alcohol
consumption,
physical
inactivity,
depression)
weaker
obesity.
45–60%
excess
mortality
attributable
diseases.InterpretationObesity
might
important
development
ageing.
Tackling
mechanisms
could
potentially
help
reduce
burden
resulting
epidemic.FundingWellcome
Trust,
Medical
Research
Council,
US
National
Institute
Aging,
Academy
Finland,
Foundation
Cardiovascular
Research.TranslationsFor
German
translations
abstract
see
Supplementary
Materials
section.
Frontiers in Immunology,
Journal Year:
2023,
Volume and Issue:
14
Published: March 8, 2023
Autoimmune
hepatitis
(AIH),
primary
biliary
cholangitis
(PBC),
sclerosing
(PSC),
and
IgG4-related
(IgG4-SC)
are
the
four
main
forms
of
autoimmune
liver
diseases
(AILDs),
which
all
defined
by
an
aberrant
immune
system
attack
on
liver.
Most
previous
studies
have
shown
that
apoptosis
necrosis
two
major
modes
hepatocyte
death
in
AILDs.
Recent
reported
inflammasome-mediated
pyroptosis
is
critical
for
inflammatory
response
severity
injury
This
review
summarizes
our
present
understanding
inflammasome
activation
function,
as
well
connections
among
inflammasomes,
pyroptosis,
AILDs,
thus
highlighting
shared
features
across
disease
models
gaps
knowledge.
In
addition,
we
summarize
correlation
NLRP3
liver-gut
axis,
injury,
intestinal
barrier
disruption
PBC
PSC.
We
differences
microbial
metabolic
characteristics
between
PSC
IgG4-SC,
highlight
uniqueness
IgG4-SC.
explore
different
roles
acute
chronic
cholestatic
complex
controversial
crosstalk
various
types
cell
also
discuss
most
up-to-date
developments
inflammasome-
pyroptosis-targeted
medicines
disorders.
European Journal of Immunology,
Journal Year:
2023,
Volume and Issue:
53(12)
Published: April 30, 2023
Recent
rapid
progress
in
key
technological
advances,
including
the
broader
accessibility
of
single-cell
"omic"
approaches,
have
allowed
immunologists
to
gain
important
novel
insights
into
contributions
individual
immune
cells
protective
immunity
and
immunopathologies.
These
also
taught
us
that
there
is
still
much
uncover
about
(cellular)
networks
underlying
responses.
For
example,
last
decade,
studies
on
a
component
innate
immunity,
complement
system,
defined
intracellularly
active
(the
complosome)
as
orchestrator
normal
cell
physiology.
This
added
an
unexpected
facet
biology
complement,
which
was
long
considered
fully
explored.
Here,
we
will
summarize
succinctly
known
activation
modes
functions
complosome
provide
perspective
origins
intracellular
complement.
We
make
case
for
extending
assessments
complotype,
inherited
landscape
common
variants
genes,
complosome,
reassessing
patients
with
serum
deficiencies
perturbations.
Finally,
discuss
where
see
current
opportunities
hurdles
dissecting
compartmentalization
activities
toward
better
understanding
their
cellular
function
health
disease.
Biomedicine & Pharmacotherapy,
Journal Year:
2024,
Volume and Issue:
175, P. 116724 - 116724
Published: May 17, 2024
Metabolic
dysfunction-associated
steatotic
liver
disease
(MASLD)
has
become
one
of
the
most
prevalent
diseases
worldwide,
and
its
occurrence
is
strongly
associated
with
obesity,
insulin
resistance
(IR),
genetics,
metabolic
stress.
Ranging
from
simple
fatty
to
steatohepatitis
(MASH),
even
severe
complications
such
as
fibrosis
advanced
cirrhosis
or
hepatocellular
carcinoma,
underlying
mechanisms
MASLD
progression
are
complex
involve
multiple
cellular
mediators
related
signaling
pathways.
Pattern
recognition
receptors
(PRRs)
innate
immune
system,
including
Toll-like
(TLRs),
C-type
lectin
(CLRs),
NOD-like
(NLRs),
RIG-like
(RLRs),
DNA
receptors,
have
been
demonstrated
potentially
contribute
pathogenesis
for
MASLD.
Their
pathways
can
induce
inflammation,
mediate
oxidative
stress,
affect
gut
microbiota
balance,
ultimately
resulting
in
hepatic
steatosis,
inflammatory
injury
fibrosis.
Here
we
review
available
literature
regarding
involvement
PRR-associated
signals
pathogenic
clinical
features
MASLD,
vitro
animal
models
We
also
discuss
emerging
targets
PRRs
drug
developments
that
involved
agent
therapies
intended
arrest
reverse
progression,
thus
enabling
refinement
therapeutic
accelerate
development.
The Journal of Immunology,
Journal Year:
2024,
Volume and Issue:
212(7), P. 1043 - 1050
Published: March 18, 2024
Abstract
NAD+
biology
is
involved
in
controlling
redox
balance,
functioning
as
a
coenzyme
numerous
enzymatic
reactions,
and
cofactor
for
Sirtuin
enzymes
substrate
multiple
regulatory
enzyme
reactions
within
outside
the
cell.
At
same
time,
levels
are
diminished
with
aging
consumed
during
development
of
inflammatory
autoimmune
diseases
linked
to
aberrant
immune
activation.
Direct
augmentation
via
salvage
Priess-Handler
pathways
being
investigated
putative
therapeutic
intervention
improve
healthspan
inflammation-linked
diseases.
In
this
review,
we
survey
its
pivotal
roles
regulation
immunity
inflammation.
Furthermore,
discuss
emerging
studies
evaluate
boosting
murine
models
human
diseases,
highlight
areas
research
that
remain
unresolved
understanding
mechanisms
action
these
nutritional
supplementation
strategies.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: March 27, 2024
ABSTRACT
The
levels
of
biogenesis
lysosome
organelles
complex
1
subunit
(BLOC1S1)
control
mitochondrial
and
endolysosome
organelle
homeostasis
function.
Reduced
fidelity
these
vacuolar
is
increasingly
being
recognized
as
important
in
instigating
cell-autonomous
immune
cell
activation.
We
reasoned
that
exploring
the
role
BLOC1S1
CD4
+
T
cells,
may
further
advance
our
understanding
regulatory
events
linked
to
and/or
endolysosomal
function
adaptive
immunity.
Transcript
canonical
transcription
factors
driving
polarization
response
activation
showed
that,
H
2
regulator
GATA3
phosphorylated
STAT6
were
preferentially
induced
depleted
primary
(TKO)
cells.
In
parallel,
both
receptor
IL-4,
IL-5
IL-13
markedly
absence
BLOC1S1.
At
level,
DNA
leakage
evoked
cGAS-STING
NF-kB
pathway
with
subsequent
polarization.
induction
autophagy
rapamycin
reduced
cytosolic
mtDNA
reverses
signatures.
Furthermore,
genetic
knockdown
STING
NF-κB
inhibition
ameliorated
this
cascade
TKO
Finally,
at
a
functional
mice
displayed
increased
susceptible
allergic
conditions
including
atopic
dermatitis
asthma.
conclusion,
depletion
mediated
disruption
integrity
initiate
predominant
responsive
phenotype
via
STING-NF-κB
driven
signaling
program.