International Immunopharmacology,
Journal Year:
2024,
Volume and Issue:
136, P. 112367 - 112367
Published: May 31, 2024
SLC25A19
is
a
mitochondrial
thiamine
pyrophosphate
(TPP)
carrier
that
mediates
TPP
entry
into
the
mitochondria.
has
been
recognized
to
play
crucial
role
in
many
metabolic
diseases,
but
its
cancer
not
clearly
reported.
Based
on
clinical
data
from
The
Cancer
Genome
Atlas
(TCGA),
following
parameters
were
analyzed
among
HCC
patients:
expression,
enrichment
analyses,
immune
infiltration,
ferroptosis
and
prognosis
analyses.
In
vitro,
high
expression
was
validated
by
qRT-PCR
Immunohistochemistry.
Subsequently,
series
of
cell
function
experiments,
including
CCK8,
EdU,
clone
formation,
trans-well
scratch
assays,
conducted
illustrate
effect
growth
metastasis
cells.
Meanwhile,
indicators
related
also
detected.
SCL25A19
highly
expressed
predicts
poor
prognosis.
Elevated
patients
markedly
associated
with
T
stage,
pathological
status
(PS),
tumor
(TS),
histologic
grade
(HG),
AFP.
Our
results
indicate
generally
good
predictive
diagnostic
ability.
gene
analyses
showed
significantly
correlated
fatty
acid
metabolism,
marker
genes.
vitro
experiments
have
confirmed
silencing
can
inhibit
proliferation
migration
ability
cells
induce
HCC.
conclusion,
these
findings
novel
prognostic
biomarker
invasion
HCC,
it
an
excellent
candidate
for
therapeutic
target
against
Nature Communications,
Journal Year:
2023,
Volume and Issue:
14(1)
Published: Dec. 20, 2023
Abstract
Hepatic
steatosis
is
the
result
of
imbalanced
nutrient
delivery
and
metabolism
in
liver
first
hallmark
Metabolic
dysfunction-associated
steatotic
disease
(MASLD).
MASLD
most
common
chronic
involves
accumulation
excess
lipids
hepatocytes,
inflammation,
cancer.
Mitochondria
play
central
roles
yet
specific
mitochondrial
functions
causally
linked
to
remain
unclear.
Here,
we
identify
Mitochondrial
Fission
Process
1
protein
(MTFP1)
as
a
key
regulator
metabolic
activity
liver.
Deletion
Mtfp1
hepatocytes
physiologically
benign
mice
leads
upregulation
oxidative
phosphorylation
(OXPHOS)
respiration,
independently
biogenesis.
Consequently,
liver-specific
knockout
are
protected
against
high
fat
diet-induced
dysregulation.
Additionally,
deletion
inhibits
permeability
transition
pore
opening
conferring
protection
apoptotic
damage
vivo
ex
vivo.
Our
work
uncovers
additional
MTFP1
liver,
positioning
this
gene
an
unexpected
OXPHOS
therapeutic
candidate
for
MASLD.
Scientific Reports,
Journal Year:
2024,
Volume and Issue:
14(1)
Published: Nov. 28, 2024
Cuproptosis
is
a
recently
discovered
form
of
regulated
cell
death
triggered
by
mitochondrial
copper
accumulation
and
proteotoxic
stress.
Here,
we
provide
the
first
evidence
that
glutathione
(GSH),
major
non-protein
thiol
in
cells,
acts
as
cuproptosis
inhibitor
pancreatic
ductal
adenocarcinoma
(PDAC)
cells.
Mechanistically,
GSH
inhibits
chelating
copper,
contrasting
its
role
blocking
ferroptosis
inhibiting
lipid
peroxidation.
The
classical
inducer,
ES-Cu
(elesclomol
plus
copper),
increases
protein
stability
transcription
factor
NFE2L2
(also
known
NRF2),
leading
to
upregulation
gene
expression
glutamate-cysteine
ligase
modifier
subunit
(GCLM)
catalytic
(GCLC).
GCLM
GCLC
are
rate-limiting
enzymes
synthesis,
increased
transported
into
mitochondria
via
solute
carrier
family
25
member
39
(SLC25A39)
transporter.
Consequently,
genetic
inhibition
NFE2L2-GSH-SLC25A39
pathway
enhances
cuproptosis-mediated
tumor
suppression
culture
mouse
models.
These
findings
not
only
reveal
distinct
mechanisms
ferroptosis,
but
also
suggest
potential
combination
strategy
suppress
PDAC
growth.
International Immunopharmacology,
Journal Year:
2024,
Volume and Issue:
136, P. 112367 - 112367
Published: May 31, 2024
SLC25A19
is
a
mitochondrial
thiamine
pyrophosphate
(TPP)
carrier
that
mediates
TPP
entry
into
the
mitochondria.
has
been
recognized
to
play
crucial
role
in
many
metabolic
diseases,
but
its
cancer
not
clearly
reported.
Based
on
clinical
data
from
The
Cancer
Genome
Atlas
(TCGA),
following
parameters
were
analyzed
among
HCC
patients:
expression,
enrichment
analyses,
immune
infiltration,
ferroptosis
and
prognosis
analyses.
In
vitro,
high
expression
was
validated
by
qRT-PCR
Immunohistochemistry.
Subsequently,
series
of
cell
function
experiments,
including
CCK8,
EdU,
clone
formation,
trans-well
scratch
assays,
conducted
illustrate
effect
growth
metastasis
cells.
Meanwhile,
indicators
related
also
detected.
SCL25A19
highly
expressed
predicts
poor
prognosis.
Elevated
patients
markedly
associated
with
T
stage,
pathological
status
(PS),
tumor
(TS),
histologic
grade
(HG),
AFP.
Our
results
indicate
generally
good
predictive
diagnostic
ability.
gene
analyses
showed
significantly
correlated
fatty
acid
metabolism,
marker
genes.
vitro
experiments
have
confirmed
silencing
can
inhibit
proliferation
migration
ability
cells
induce
HCC.
conclusion,
these
findings
novel
prognostic
biomarker
invasion
HCC,
it
an
excellent
candidate
for
therapeutic
target
against
