Advanced Science,
Journal Year:
2024,
Volume and Issue:
11(31)
Published: June 19, 2024
Creatine
kinases
are
essential
for
maintaining
cellular
energy
balance
by
facilitating
the
reversible
transfer
of
a
phosphoryl
group
from
ATP
to
creatine,
however,
their
role
in
mitochondrial
production
remains
unknown.
This
study
shows
creatine
kinases,
including
CKMT1A,
CKMT1B,
and
CKB,
highly
expressed
cells
relying
on
F1F0
synthase
survival.
Interestingly,
silencing
but
not
CKMT1A
or
leads
loss
sensitivity
inhibition
these
cells.
Mechanistically,
CKB
promotes
reduces
glycolytic
suppressing
calcium
(mCa
Signal Transduction and Targeted Therapy,
Journal Year:
2024,
Volume and Issue:
9(1)
Published: May 15, 2024
Abstract
Mitochondria,
with
their
intricate
networks
of
functions
and
information
processing,
are
pivotal
in
both
health
regulation
disease
progression.
Particularly,
mitochondrial
dysfunctions
identified
many
common
pathologies,
including
cardiovascular
diseases,
neurodegeneration,
metabolic
syndrome,
cancer.
However,
the
multifaceted
nature
elusive
phenotypic
threshold
dysfunction
complicate
our
understanding
contributions
to
diseases.
Nonetheless,
these
complexities
do
not
prevent
mitochondria
from
being
among
most
important
therapeutic
targets.
In
recent
years,
strategies
targeting
have
continuously
emerged
transitioned
clinical
trials.
Advanced
intervention
such
as
using
healthy
replenish
or
replace
damaged
mitochondria,
has
shown
promise
preclinical
trials
various
Mitochondrial
components,
mtDNA,
mitochondria-located
microRNA,
associated
proteins
can
be
potential
agents
augment
function
immunometabolic
diseases
tissue
injuries.
Here,
we
review
current
knowledge
pathophysiology
concrete
examples
We
also
summarize
treat
perspective
dietary
supplements
targeted
therapies,
well
translational
situation
related
pharmacology
agents.
Finally,
this
discusses
innovations
applications
transplantation
an
advanced
promising
treatment.
Nature Immunology,
Journal Year:
2022,
Volume and Issue:
23(5), P. 692 - 704
Published: April 28, 2022
Abstract
The
NLRP3
inflammasome
is
linked
to
sterile
and
pathogen-dependent
inflammation,
its
dysregulation
underlies
many
chronic
diseases.
Mitochondria
have
been
implicated
as
regulators
of
the
through
several
mechanisms
including
generation
mitochondrial
reactive
oxygen
species
(ROS).
Here,
we
report
that
electron
transport
chain
(ETC)
complex
I,
II,
III
V
inhibitors
all
prevent
activation.
Ectopic
expression
Saccharomyces
cerevisiae
NADH
dehydrogenase
(NDI1)
or
Ciona
intestinalis
alternative
oxidase,
which
can
complement
functional
loss
I
III,
respectively,
without
ROS,
rescued
activation
in
absence
endogenous
function.
Metabolomics
revealed
phosphocreatine
(PCr),
sustain
ATP
levels,
a
common
metabolite
diminished
by
ETC
inhibitors.
PCr
depletion
decreased
levels
Thus,
sustains
PCr-dependent
ATP,
but
via
ROS-independent
mechanism.
Cellular and Molecular Life Sciences,
Journal Year:
2021,
Volume and Issue:
78(13), P. 5303 - 5324
Published: May 26, 2021
Abstract
A
growing
body
of
evidence
indicates
that,
over
the
course
evolution
immune
system,
arginine
has
been
selected
as
a
node
for
regulation
responses.
An
appropriate
supply
long
associated
with
improvement
In
addition
to
being
building
block
protein
synthesis,
serves
substrate
distinct
metabolic
pathways
that
profoundly
affect
cell
biology;
especially
macrophage,
dendritic
and
T
immunobiology.
Arginine
availability,
catabolism
are
highly
interrelated
aspects
responses
their
fine-tuning
can
dictate
divergent
pro-inflammatory
or
anti-inflammatory
outcomes.
Here,
we
review
organismal
metabolism
in
humans
rodents,
essential
modulators
availability
this
semi-essential
amino
acid
cells.
We
subsequently
well-established
novel
findings
on
functional
impact
biosynthetic
catabolic
main
lineages.
Finally,
emerged
molecule
impacting
plethora
functions,
integrate
key
notions
how
disruption
perversion
is
implicated
pathologies
ranging
from
infectious
diseases
autoimmunity
cancer.
Nutrients,
Journal Year:
2021,
Volume and Issue:
13(4), P. 1238 - 1238
Published: April 9, 2021
Creatine
(Cr)
is
a
ubiquitous
molecule
that
synthesized
mainly
in
the
liver,
kidneys,
and
pancreas.
Most
of
Cr
pool
found
tissues
with
high-energy
demands.
enters
target
cells
through
specific
symporter
called
Na+/Cl−-dependent
transporter
(CRT).
Once
within
cells,
creatine
kinase
(CK)
catalyzes
reversible
transphosphorylation
reaction
between
[Mg2+:ATP4−]2−
to
produce
phosphocreatine
(PCr)
[Mg2+:ADP3−]−.
We
aimed
perform
comprehensive
bioinformatics-assisted
review
most
recent
research
findings
regarding
metabolism.
Specifically,
several
public
databases,
repositories,
bioinformatics
tools
were
utilized
for
this
endeavor.
Topics
biological
complexity
ranging
from
structural
biology
cellular
dynamics
addressed
herein.
In
sense,
we
sought
address
certain
pre-specified
questions
including:
(i)
What
happens
when
transported
into
cells?
(ii)
How
CK/PCr
system
involved
bioenergetics?
(iii)
compartmentalized
throughout
cell?
(iv)
role
amongst
different
tissues?
(v)
basis
transport?
Under
allostasis
paradigm,
physiologically
essential
life
(cell
survival,
growth,
proliferation,
differentiation,
migration/motility)
by
providing
an
evolutionary
advantage
rapid,
local,
temporal
support
energy-
mechanical-dependent
processes.
Thus,
suggest
acts
as
dynamic
biosensor
based
on
chemo-mechanical
energy
transduction,
which
might
explain
why
dysregulation
metabolism
contributes
wide
range
diseases
besides
mitigating
effect
supplementation
may
have
some
these
disease
states.
Cells,
Journal Year:
2021,
Volume and Issue:
10(9), P. 2371 - 2371
Published: Sept. 9, 2021
In
solid
tumours,
cancer
cells
exist
within
hypoxic
microenvironments,
and
their
metabolic
adaptation
to
this
hypoxia
is
driven
by
HIF-1
transcription
factor,
which
overexpressed
in
a
broad
range
of
human
cancers.
HIF
inhibitors
are
under
pre-clinical
investigation
clinical
trials,
but
there
evidence
that
can
adapt
metabolically
inhibition,
would
provide
potential
route
for
drug
resistance.
Here,
we
review
accumulating
such
adaptions
carbohydrate
creatine
metabolism
other
HIF-1-independent
mechanisms
might
allow
cancers
survive
despite
anti-HIF-1
therapy.
These
include
pathways
glucose,
glutamine,
lipid
metabolism;
epigenetic
mechanisms;
post-translational
protein
modifications;
spatial
reorganization
enzymes;
signalling
as
Myc,
PI3K-Akt,
2-hyxdroxyglutarate
AMP-activated
kinase
(AMPK);
activation
the
HIF-2
pathway.
All
these
should
be
investigated
future
work
on
bypass
principle,
agents
targeted
toward
HIF-1β
rather
than
HIF-1α
advantageous,
both
require
activation.
However,
also
aryl
hydrocarbon
nuclear
transporter
(ARNT),
has
functions
many
tissues,
so
off-target
effects
expected.
general,
therapy
inhibition
will
need
careful
attention
resistance
mechanisms.
Nature Metabolism,
Journal Year:
2022,
Volume and Issue:
4(2), P. 190 - 202
Published: Feb. 14, 2022
Abstract
The
mechanisms
promoting
disturbed
white
adipocyte
function
in
obesity
remain
largely
unclear.
Herein,
we
integrate
adipose
tissue
(WAT)
metabolomic
and
transcriptomic
data
from
clinical
cohorts
find
that
the
WAT
phosphocreatine/creatine
ratio
is
increased
creatine
kinase-B
expression
activity
decreased
obese
state.
In
human
vitro
murine
vivo
models,
demonstrate
phosphocreatine
metabolism
adipocytes
alters
adenosine
monophosphate-activated
protein
kinase
via
effects
on
triphosphate/adenosine
diphosphate
levels,
independently
of
beigeing.
This
disturbance
promotes
a
pro-inflammatory
profile
characterized,
part,
by
chemokine
(C-C
motif)
ligand
2
(CCL2)
production.
These
suggest
system
links
cellular
energy
shuttling
with
responses
adipocytes.
Our
findings
provide
unexpected
perspectives
driving
inflammation
may
present
avenues
to
target
dysfunction.
