Preventive Nutrition and Food Science,
Год журнала:
2022,
Номер
27(4), С. 335 - 346
Опубликована: Дек. 31, 2022
Metabolic
rewiring
and
epigenetic
reprogramming
are
closely
inter-related,
mutually
regulate
each
other
to
control
cell
growth
in
cancer
initiation,
promotion,
progression,
metastasis.Epigenetics
plays
a
crucial
role
regulating
normal
cellular
functions
as
well
pathological
conditions
many
diseases,
including
cancer.Conversely,
certain
mitochondrial
metabolites
considered
essential
cofactors
regulators
of
mechanisms.Furthermore,
dysregulation
metabolism
promotes
tumor
reprograms
the
cells
produce
bioenergy
needed
support
proliferation.Hence,
metabolic
which
alters
metabolites/epigenetic
cofactors,
would
drive
landscape,
DNA
methylation
histone
modification,
that
could
lead
progression.Recognizing
diverse
array
benefits
phytochemicals,
they
gaining
increasing
interest
interception
treatment.One
significant
mechanisms
treatment
by
phytochemicals
is
key
pathways
remodeling
epigenetics.This
review
focuses
on
epigenetics
investigates
potential
can
mitigate
cancer.
Nature reviews. Cancer,
Год журнала:
2023,
Номер
23(3), С. 156 - 172
Опубликована: Янв. 19, 2023
Few
metabolites
can
claim
a
more
central
and
versatile
role
in
cell
metabolism
than
acetyl
coenzyme
A
(acetyl-CoA).
Acetyl-CoA
is
produced
during
nutrient
catabolism
to
fuel
the
tricarboxylic
acid
cycle
essential
building
block
for
fatty
isoprenoid
biosynthesis.
It
also
functions
as
signalling
metabolite
substrate
lysine
acetylation
reactions,
enabling
modulation
of
protein
response
acetyl-CoA
availability.
Recent
years
have
seen
exciting
advances
our
understanding
normal
physiology
cancer,
buoyed
by
new
mouse
models,
vivo
stable-isotope
tracing
approaches
improved
methods
measuring
acetyl-CoA,
including
specific
subcellular
compartments.
Efforts
target
metabolic
enzymes
are
advancing,
with
one
therapeutic
agent
targeting
synthesis
receiving
approval
from
US
Food
Drug
Administration.
In
this
Review,
we
give
an
overview
regulation
cancer
relevance
major
pathways
which
participates.
We
further
discuss
recent
tissues
tumours
potential
these
therapeutically.
conclude
commentary
on
emerging
nodes
that
may
impact
biology.
Protein
posttranslational
modifications
(PTMs)
refer
to
the
breaking
or
generation
of
covalent
bonds
on
backbones
amino
acid
side
chains
proteins
and
expand
diversity
proteins,
which
provides
basis
for
emergence
organismal
complexity.
To
date,
more
than
650
types
protein
modifications,
such
as
most
well-known
phosphorylation,
ubiquitination,
glycosylation,
methylation,
SUMOylation,
short-chain
long-chain
acylation
redox
irreversible
have
been
described,
inventory
is
still
increasing.
By
changing
conformation,
localization,
activity,
stability,
charges,
interactions
with
other
biomolecules,
PTMs
ultimately
alter
phenotypes
biological
processes
cells.
The
homeostasis
important
human
health.
Abnormal
may
cause
changes
in
properties
loss
functions,
are
closely
related
occurrence
development
various
diseases.
In
this
review,
we
systematically
introduce
characteristics,
regulatory
mechanisms,
functions
health
addition,
therapeutic
prospects
diseases
by
targeting
associated
enzymes
also
summarized.
This
work
will
deepen
understanding
promote
discovery
diagnostic
prognostic
markers
drug
targets
In
eukaryotic
cells,
DNA
is
tightly
packed
with
the
help
of
histone
proteins
into
chromatin.
Chromatin
architecture
can
be
modified
by
various
post-translational
modifications
proteins.
For
almost
60
years
now,
studies
on
lysine
acetylation
have
unraveled
contribution
this
acylation
to
an
open
chromatin
state
increased
accessibility,
permissive
for
gene
expression.
Additional
complexity
emerged
from
discovery
other
types
acylations.
The
acyl
group
donors
are
products
cellular
metabolism,
and
distinct
acylations
link
metabolic
a
cell
contribute
adaptation
through
changes
in
Currently,
technical
challenges
limit
our
full
understanding
actual
impact
most
dynamics
their
biological
relevance.
review,
we
summarize
art
provide
overview
approaches
overcome
these
challenges.
We
further
discuss
concept
subnuclear
niches
that
could
regulate
local
CoA
availability
thus
couple
metabolisms
epigenome.
Abstract
Histones
are
DNA‐binding
basic
proteins
found
in
chromosomes.
After
the
histone
translation,
its
amino
tail
undergoes
various
modifications,
such
as
methylation,
acetylation,
phosphorylation,
ubiquitination,
malonylation,
propionylation,
butyrylation,
crotonylation,
and
lactylation,
which
together
constitute
“histone
code.”
The
relationship
between
their
combination
biological
function
can
be
used
an
important
epigenetic
marker.
Methylation
demethylation
of
same
residue,
acetylation
deacetylation,
phosphorylation
dephosphorylation,
even
methylation
different
residues
cooperate
or
antagonize
with
each
other,
forming
a
complex
network.
Histone‐modifying
enzymes,
cause
numerous
codes,
have
become
hot
topic
research
on
cancer
therapeutic
targets.
Therefore,
thorough
understanding
role
post‐translational
modifications
(PTMs)
cell
life
activities
is
very
for
preventing
treating
human
diseases.
In
this
review,
several
most
thoroughly
studied
newly
discovered
PTMs
introduced.
Furthermore,
we
focus
histone‐modifying
enzymes
carcinogenic
potential,
abnormal
modification
sites
tumors,
multiple
essential
molecular
regulation
mechanism.
Finally,
summarize
missing
areas
current
point
out
direction
future
research.
We
hope
to
provide
comprehensive
promote
further
field.
The
metabolite
acetyl-CoA
is
necessary
for
both
lipid
synthesis
in
the
cytosol
and
histone
acetylation
nucleus.
two
canonical
precursors
to
nuclear-cytoplasmic
compartment
are
citrate
acetate,
which
processed
by
ATP-citrate
lyase
(ACLY)
acyl-CoA
synthetase
short-chain
2
(ACSS2),
respectively.
It
unclear
whether
other
substantial
routes
nuclear-cytosolic
exist.
To
investigate
this,
we
generated
cancer
cell
lines
lacking
ACLY
ACSS2
[double
knockout
(DKO)
cells].
Using
stable
isotope
tracing,
show
that
glucose
fatty
acids
contribute
pools
DKO
cells
acetylcarnitine
shuttling
can
transfer
two-carbon
units
from
mitochondria
cytosol.
Further,
absence
of
ACLY,
feed
acid
a
carnitine
responsive
acetyltransferase
(CrAT)-dependent
manner.
data
define
as
an
ACLY-
ACSS2-independent
precursor
support
acetylation,
synthesis,
growth.
