International Journal of Molecular Sciences,
Journal Year:
2018,
Volume and Issue:
19(3), P. 818 - 818
Published: March 12, 2018
The
mechanistic
target
of
rapamycin
complex
1
(mTORC1)
coordinates
cellular
growth
and
metabolism
with
environmental
inputs
to
ensure
that
cells
grow
only
under
favourable
conditions.
When
active,
mTORC1
stimulates
biosynthetic
pathways
including
protein,
lipid
nucleotide
synthesis
inhibits
catabolism
through
repression
the
autophagic
pathway,
thereby
promoting
cell
proliferation.
recruitment
lysosomal
surface
has
been
shown
be
essential
for
its
activation.
This
finding
significantly
enhanced
our
knowledge
regulation
focused
attention
field
on
lysosome
as
a
signalling
hub
which
several
homeostatic
pathways.
intriguing
localisation
organelle
plays
crucial
role
in
enables
feedback
autophagy
biogenesis,
thus
leading
enact
precise
spatial
temporal
control
growth.
review
will
cover
interactions
take
place
lysosomes
cross-talk
exists
between
activity
function.
Essays in Biochemistry,
Journal Year:
2017,
Volume and Issue:
61(6), P. 585 - 596
Published: Dec. 12, 2017
Autophagy
is
a
vital
lysosomal
degradation
pathway
that
serves
as
quality
control
mechanism.
It
rids
the
cell
of
damaged,
toxic
or
excess
cellular
components,
which
if
left
to
persist
could
be
detrimental
cell.
also
recycling
maintain
protein
synthesis
under
starvation
conditions.
A
key
initial
event
in
autophagy
formation
autophagosome,
unique
double-membrane
organelle
engulfs
cytosolic
cargo
destined
for
degradation.
This
step
mediated
by
serine/threonine
kinase
ULK1
(unc-51-like
1),
functions
complex
with
at
least
three
partners:
FIP200
(focal
adhesion
family
interacting
200
kDa),
ATG
(autophagy-related
protein)
13
(ATG13),
and
ATG101.
In
this
artcile,
we
focus
on
regulation
during
initiation.
The
pattern
upstream
pathways
converge
suggests
acts
node,
converting
multiple
signals
into
autophagosome
formation.
Here,
review
our
current
understanding
turn
discuss
what
happens
downstream,
once
becomes
activated.
Signal Transduction and Targeted Therapy,
Journal Year:
2022,
Volume and Issue:
7(1)
Published: Aug. 13, 2022
Regulated
cell
death
(RCD),
also
well-known
as
programmed
(PCD),
refers
to
the
form
of
that
can
be
regulated
by
a
variety
biomacromolecules,
which
is
distinctive
from
accidental
(ACD).
Accumulating
evidence
has
revealed
RCD
subroutines
are
key
features
tumorigenesis,
may
ultimately
lead
establishment
different
potential
therapeutic
strategies.
Hitherto,
targeting
with
pharmacological
small-molecule
compounds
been
emerging
promising
avenue,
rapidly
progressed
in
many
types
human
cancers.
Thus,
this
review,
we
focus
on
summarizing
not
only
apoptotic
and
autophagy-dependent
signaling
pathways,
but
crucial
pathways
other
subroutines,
including
necroptosis,
pyroptosis,
ferroptosis,
parthanatos,
entosis,
NETosis
lysosome-dependent
(LCD)
cancer.
Moreover,
further
discuss
current
situation
several
improve
cancer
treatment,
such
single-target,
dual
or
multiple-target
compounds,
drug
combinations,
some
new
strategies
would
together
shed
light
future
directions
attack
vulnerabilities
drugs
for
purposes.
FEBS Letters,
Journal Year:
2020,
Volume and Issue:
595(8), P. 976 - 1002
Published: Dec. 12, 2020
Most
of
the
genetic
information
has
been
lost
or
transferred
to
nucleus
during
evolution
mitochondria.
Nevertheless,
mitochondria
have
retained
their
own
genome
that
is
essential
for
oxidative
phosphorylation
(OXPHOS).
In
mammals,
a
gene‐dense
circular
mitochondrial
DNA
(mtDNA)
about
16.5
kb
encodes
13
proteins,
which
constitute
only
1%
proteome.
Mammalian
mtDNA
present
in
thousands
copies
per
cell
and
mutations
often
affect
fraction
them.
pathogenic
human
are
recessive
cause
OXPHOS
defects
if
above
certain
critical
threshold.
However,
emerging
evidence
strongly
suggests
proportion
mutated
not
determinant
disease
but
also
absolute
copy
number
matters.
this
review,
we
critically
discuss
current
knowledge
role
regulation
various
types
diseases,
including
disorders,
neurodegenerative
disorders
cancer,
ageing.
We
provide
an
overview
new
exciting
therapeutic
strategies
directly
manipulate
restore
diseases.
Signal Transduction and Targeted Therapy,
Journal Year:
2023,
Volume and Issue:
8(1)
Published: Oct. 2, 2023
The
mammalian
target
of
rapamycin
(mTOR)
is
a
protein
kinase
that
controls
cellular
metabolism,
catabolism,
immune
responses,
autophagy,
survival,
proliferation,
and
migration,
to
maintain
homeostasis.
mTOR
signaling
cascade
consists
two
distinct
multi-subunit
complexes
named
complex
1/2
(mTORC1/2).
catalyzes
the
phosphorylation
several
critical
proteins
like
AKT,
C,
insulin
growth
factor
receptor
(IGF-1R),
4E
binding
1
(4E-BP1),
ribosomal
S6
(S6K),
transcription
EB
(TFEB),
sterol-responsive
element-binding
(SREBPs),
Lipin-1,
Unc-51-like
autophagy-activating
kinases.
plays
central
role
in
regulating
translation,
lipid
synthesis,
nucleotide
biogenesis
lysosomes,
nutrient
sensing,
signaling.
emerging
pieces
evidence
have
revealed
constitutive
activation
pathway
due
mutations/amplification/deletion
either
its
(mTORC1
mTORC2)
or
upstream
targets
responsible
for
aging,
neurological
diseases,
human
malignancies.
Here,
we
provide
detailed
structure
mTOR,
complexes,
comprehensive
regulators,
as
well
downstream
effectors
cascades
biomolecules,
autophagy.
Additionally,
summarize
potential
long
noncoding
RNAs
(lncRNAs)
an
important
modulator
Importantly,
highlighted
disorders,
cancers,
cancer
stem
cells,
drug
resistance.
discuss
developments
therapeutic
targeting
with
improved
anticancer
efficacy
benefit
patients
clinics.
Frontiers in Cell and Developmental Biology,
Journal Year:
2018,
Volume and Issue:
6
Published: Oct. 12, 2018
Autophagy
is
a
tightly
regulated
catabolic
process
wherein
cells
under
stress
sequester
cytosolic
constituents
like
damaged
proteins
and
organelles
in
double-membrane
vesicles
called
autophagosomes.
The
autophagosomes
degrade
their
cargo
by
lysosomal
proteolysis
generating
raw
materials
for
the
biosynthesis
of
vital
macromolecules.
One
initial
steps
assembly
from
pre-autophagic
structures
recruitment
activation
class
III
phosphatidylinositol
3-kinase
complex
consisting
Beclin
1
(BECN1),
VPS34,
VPS15
ATG14
proteins.
Evidence
indicate
that
phosphorylation
ubiquitination
BECN1
at
an
array
residues
fine-tune
responses
to
diverse
autophagy
modulating
stimuli
helps
maintaining
balance
between
pro-survival
pro-apoptotic
responses.
In
this
mini-review
we
will
discuss
importance
distinct
events,
signaling
pathways
kinases
involved
role
regulation
autophagy.
International Journal of Molecular Sciences,
Journal Year:
2020,
Volume and Issue:
21(9), P. 3289 - 3289
Published: May 6, 2020
Autophagy
is
a
catabolic
process
for
unnecessary
or
dysfunctional
cytoplasmic
contents
by
lysosomal
degradation
pathways.
implicated
in
various
biological
processes
such
as
programmed
cell
death,
stress
responses,
elimination
of
damaged
organelles
and
development.
The
role
autophagy
crucial
mediator
has
been
clarified
expanded
the
pathological
response
to
redox
signalling.
major
sensor
Reactive
oxygen
species
(ROS)
are
highly
reactive
molecules
that
generated
by-products
cellular
metabolism,
principally
mitochondria.
Mitochondrial
ROS
(mROS)
beneficial
detrimental
cells
depending
on
their
concentration
location.
mROS
function
messengers
intracellular
signalling
at
physiologically
low
level,
whereas
excessive
production
causes
oxidative
damage
constituents
thus
incurs
death.
Hence,
balance
autophagy-related
adaptation
death
important
comprehend
signalling-related
pathogenesis.
In
this
review,
we
attempt
provide
an
overview
basic
mechanism
context
pathology.
Frontiers in Cell and Developmental Biology,
Journal Year:
2021,
Volume and Issue:
8
Published: Jan. 12, 2021
Metabolic
reprogramming
has
been
widely
recognized
as
a
hallmark
of
malignancy.
The
uptake
and
metabolism
amino
acids
are
aberrantly
upregulated
in
many
cancers
that
display
addiction
to
particular
acids.
Amino
facilitate
the
survival
proliferation
cancer
cells
under
genotoxic,
oxidative,
nutritional
stress.
Thus,
targeting
acid
is
becoming
potential
therapeutic
strategy
for
patients.
In
this
review,
we
will
systematically
summarize
recent
progress
malignancy
discuss
their
interconnection
with
mammalian
target
rapamycin
complex
1
(mTORC1)
signaling,
epigenetic
modification,
tumor
growth
immunity,
ferroptosis.
Finally,
highlight
applications.
Cancers,
Journal Year:
2019,
Volume and Issue:
11(10), P. 1422 - 1422
Published: Sept. 24, 2019
Autophagy
is
a
process
of
self-degradation
that
enables
the
cell
to
survive
when
faced
with
starvation
or
stressful
conditions.
The
mechanistic
target
rapamycin
(mTOR),
also
known
as
mammalian
rapamycin,
plays
critical
role
in
maintaining
balance
between
cellular
anabolism
and
catabolism.
mTOR
complex
1
(mTORC1)
was
unveiled
master
regulator
autophagy
since
inhibition
mTORC1
required
initiate
process.
Evidence
has
emerged
recent
years
indicate
directly
regulates
subsequent
steps
process,
including
nucleation,
autophagosome
elongation,
maturation
termination.
By
phosphorylating
select
protein
targets
core
machinery
and/or
their
regulators,
can
alter
functions,
increase
proteasomal
degradation
modulate
acetylation
status,
which
key
switch
Moreover,
it
phosphorylates
alters
subcellular
localization
transcription
factors
suppress
expression
genes
needed
for
formation
lysosome
biogenesis.
purpose
this
review
article
critically
analyze
current
literatures
provide
an
integrated
view
how
various
Annals of the New York Academy of Sciences,
Journal Year:
2020,
Volume and Issue:
1467(1), P. 3 - 20
Published: Jan. 27, 2020
Abstract
Macroautophagy
is
a
lysosomal
degradative
pathway
or
recycling
process
that
maintains
cellular
homeostasis.
This
autophagy
involves
series
of
sequential
processing
events,
such
as
initiation;
elongation
and
nucleation
the
isolation
membrane;
cargo
recruitment
maturation
autophagosome
(AP);
transport
AP;
docking
fusion
AP
with
late
endosome
lysosome;
regeneration
lysosome
by
autophagic
reformation
cycle.
These
events
are
critically
coordinated
action
set
several
key
components,
including
autophagy‐related
proteins
(Atg),
regulated
intricate
networks,
mechanistic
target
rapamycin
(mTOR),
master
regulator
autophagy,
well
mTOR‐independent
signaling
pathways.
Among
pathways,
transient
receptor
potential
(TRP)
calcium
ion
channel
TRPML
(mucolipin)
subfamily
emerging
an
important
to
modulate
biogenesis
autophagy.
review
discusses
recent
advances
in
elucidating
molecular
mechanisms
regulation
process.
Understanding
these
may
ultimately
allow
scientists
clinicians
control
this
order
improve
human
health.
Journal of Oncology,
Journal Year:
2020,
Volume and Issue:
2020, P. 1 - 11
Published: March 9, 2020
Breast
cancer
is
the
with
highest
prevalence
in
women
and
number-one
cause
of
mortality
worldwide.
Cell
transduction
a
fundamental
process
development
progression
cancer.
Modifications
various
cell
signalling
pathways
promote
tumour
proliferation,
progression,
survival.
The
PI3K/Akt/mTOR
pathway
an
example
that,
it
involved
growth,
survival,
motility,
metabolism,
immune
response
regulation.
Activation
this
one
main
causes
resistance
to
antitumour
therapies.
This
makes
crucial
object
study
for
understanding
disease.
Thus,
may
have
role
as
potential
therapeutic
target,
well
prognostic
diagnostic
value,
patients
breast
Despite
existence
selective
inhibitors
current
clinical
trials,
cellular
mechanisms
are
not
yet
known.
present
review
aims
understand
state
important
disease
paths
that
must
be
forged.