bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Сен. 21, 2024
Abstract
Proliferating
tumor
cells
take
up
glutamine
for
anabolic
processes
engendering
deficiency
in
the
microenvironment.
How
this
might
impact
immune
is
not
well
understood.
Using
multiple
mouse
models
of
soft
tissue
sarcomas,
antagonists,
as
genetic
and
pharmacological
inhibition
utilization,
we
found
that
number
frequency
conventional
dendritic
(cDC)
dependent
on
microenvironmental
levels.
cDCs
comprise
two
distinct
subsets
–
cDC1
cDC2,
with
former
subset
playing
a
critical
role
antigen
cross-presentation
immunity.
While
both
show
dependence
Glutamine,
cDC1s
are
particularly
sensitive.
Notably,
antagonism
did
reduce
DC
precursors
but
decreased
proliferation
survival
cDC1s.
Further
studies
suggest
nutrient
sensing
mTOR
signaling
pathway
process.
Taken
together,
these
findings
uncover
coopted
by
tumors
to
escape
responses.
One
Sentence
Summary
Type
1
require
maintain
their
non-lymphoid
tissue.
Significance
Immune
evasion
key
hallmark
cancer;
however,
underlying
pathways
diverse,
tumor-specific
fully
elucidated.
Many
avidly
import
support
needs,
creating
glutamine-deficient
microenvironment
(TME).
Herein,
using
depletion
TME
leads
reduced
type
cell
adaptive
This
work
paradigm
how
metabolism
can
regulate
anti-tumor
responses
will
be
foundational
future
efforts
targeting
cancer
immunotherapy.
Biomolecules,
Год журнала:
2023,
Номер
13(9), С. 1304 - 1304
Опубликована: Авг. 25, 2023
Calcium
(Ca2+)
ions
act
as
a
second
messenger,
regulating
several
cell
functions.
Mitochondria
are
critical
organelles
for
the
regulation
of
intracellular
Ca2+.
Mitochondrial
calcium
(mtCa2+)
uptake
is
ensured
by
presence
in
inner
mitochondrial
membrane
(IMM)
uniporter
(MCU)
complex,
macromolecular
structure
composed
pore-forming
and
regulatory
subunits.
MtCa2+
plays
crucial
role
oxidative
metabolism
death.
A
lot
evidence
demonstrates
that
dysregulation
mtCa2+
homeostasis
can
have
serious
pathological
outcomes.
In
this
review,
we
briefly
discuss
molecular
function
MCU
complex
then
focus
our
attention
on
human
diseases
which
dysfunction
has
been
shown.
Cancer Drug Resistance,
Год журнала:
2024,
Номер
unknown
Опубликована: Март 15, 2024
Globally,
cancer,
as
a
major
public
health
concern,
poses
severe
threat
to
people’s
well-being.
Advanced
and
specialized
therapies
can
now
cure
the
majority
of
people
with
early-stage
cancer.
However,
emerging
resistance
traditional
novel
chemotherapeutic
drugs
remains
serious
issue
in
clinical
medicine.
Chemoresistance
often
leads
cancer
recurrence,
metastasis,
increased
mortality,
accounting
for
90%
chemotherapy
failures.
Thus,
it
is
important
understand
molecular
mechanisms
chemoresistance
find
therapeutic
approaches
treatment.
Among
several
factors
responsible
chemoresistance,
calcium
(Ca2+)
dysregulation
plays
significant
role
progression
chemoresistance.
Therefore,
targeting
this
derailed
Ca2+
signalling
therapy
has
become
an
research
area.
Of
note,
signal
its
proteins
are
multifaceted
potent
tool
by
which
cells
achieve
specific
outcomes.
Depending
on
cell
survival
needs,
either
upregulated
or
downregulated
both
chemosensitive
chemoresistant
cells.
Consequently,
appropriate
treatment
should
be
selected
based
dysregulation.
This
review
discusses
channels,
pumps,
exchangers.
Furthermore,
we
have
emphasised
strategies.
In
conclusion,
process.
Methods
such
site-specific
drug
delivery,
target-based
drug-designing,
two
more
simultaneously
may
explored;
however,
further
studies
essential
validate
blockers’
anti-cancer
efficacy.
Expert Review of Proteomics,
Год журнала:
2025,
Номер
22(1), С. 19 - 33
Опубликована: Янв. 2, 2025
Introduction
Mitochondria
contain
multiple
pathways
including
energy
metabolism
and
several
signaling
synthetic
pathways.
Mitochondrial
proteomics
is
highly
valuable
for
studying
diseases
inherited
metabolic
disorders,
complex
common
disorders
like
neurodegeneration,
diabetes
cancer,
since
they
all
to
some
degree
have
mitochondrial
underpinnings.
Metabolic
adaptations
are
essential
for
survival.
The
mitochondrial
calcium
uniporter
plays
a
key
role
in
coordinating
metabolic
homeostasis
by
regulating
pathways
and
signaling.
However,
comprehensive
analysis
of
uniporter-regulated
has
remained
unexplored.
Here,
we
investigate
consequences
loss
gain
function
using
knockout
cells
fibrolamellar
carcinoma
(FLC),
which
demonstrate
to
have
elevated
levels.
We
find
that
branched-chain
amino
acid
(BCAA)
catabolism
the
urea
cycle
pathways.
Reduced
boosts
expression
BCAA
genes
enzyme
ornithine
transcarbamylase.
In
contrast,
high
activity
FLC
suppresses
their
expression.
This
suppression
is
mediated
transcription
factor
KLF15,
master
regulator
liver
metabolism.
Thus,
central
FLC-associated
changes,
including
hyperammonemia.
Our
study
identifies
an
important
adaptation
through
transcriptional
regulation
metabolism
elucidates
its
importance
ammonia
