Cold Spring Harbor Perspectives in Biology,
Journal Year:
2019,
Volume and Issue:
12(4), P. a034074 - a034074
Published: April 8, 2019
The
functional
health
of
the
proteome
is
determined
by
properties
proteostasis
network
(PN)
that
regulates
protein
synthesis,
folding,
macromolecular
assembly,
translocation,
and
degradation.
In
eukaryotes,
PN
also
integrates
biogenesis
across
compartments
within
cell
between
tissues
metazoans
for
organismal
longevity.
Additionally,
in
metazoans,
stability
proteins
optimized
development
yet
declines
throughout
aging,
accelerating
risk
misfolding,
aggregation,
cellular
dysfunction.
Here,
I
describe
cell-nonautonomous
regulation
tissue
communication
stress-response
pathways.
These
systems
are
robust
from
through
reproductive
maturity
genetically
programmed
to
decline
abruptly
early
adulthood
repression
heat
shock
response
other
cell-protective
stress
responses,
thus
compromising
ability
cells
properly
buffer
against
cumulative
damage
during
aging.
While
failure
multiple
quality
control
processes
aging
challenges
function
health,
genetic
studies,
identification
small-molecule
regulators
suggests
strategies
can
be
employed
reset
with
potential
benefit
on
Frontiers in Molecular Biosciences,
Journal Year:
2019,
Volume and Issue:
6
Published: March 12, 2019
The
endoplasmic
reticulum
(ER)
is
an
important
site
for
protein
folding
and
maturation
in
eukaryotes.
cellular
requirement
to
synthesize
proteins
within
the
ER
matched
by
its
capacity.
However,
physiological
demands
or
aberrations
may
result
imbalance
which
can
lead
accumulation
of
misfolded
protein,
also
known
as
"ER
stress."
unfolded
response
(UPR)
a
cell-signaling
system
that
readjusts
capacity
restore
homeostasis.
key
UPR
signal
activator,
IRE1,
responds
stress
propagating
from
cytosol.
Here,
we
discuss
structural
molecular
basis
IRE1
signaling,
with
particular
focus
on
novel
mechanistic
advances.
We
draw
comparison
between
recently
proposed
allosteric
model
induction
role
Hsp70
during
polypeptide
import
mitochondrial
matrix.
The Journal of Cell Biology,
Journal Year:
2019,
Volume and Issue:
218(10), P. 3171 - 3187
Published: Sept. 19, 2019
Protein
folding
is
inherently
error
prone,
especially
in
the
endoplasmic
reticulum
(ER).
Even
with
an
elaborate
network
of
molecular
chaperones
and
protein
facilitators,
misfolding
can
occur
quite
frequently.
To
maintain
homeostasis,
eukaryotes
have
evolved
a
series
quality-control
checkpoints.
When
secretory
pathway
pathways
fail,
stress
response
pathways,
such
as
unfolded
(UPR),
are
induced.
In
addition,
ER,
which
initial
hub
biogenesis
pathway,
triages
misfolded
proteins
by
delivering
substrates
to
proteasome
or
lysosome/vacuole
through
ER-associated
degradation
(ERAD)
ER-phagy.
Some
escape
ER
instead
selected
for
Golgi
quality
control.
These
targeted
after
retrieval
delivery
lysosome/vacuole.
Here,
we
discuss
how
these
guardian
function,
their
activities
intersect
upon
induction
UPR,
decisions
made
dispose
pathway.
Cold Spring Harbor Perspectives in Biology,
Journal Year:
2019,
Volume and Issue:
12(1), P. a033951 - a033951
Published: March 4, 2019
Gopal
G.
Jayaraj,
Mark
S.
Hipp
and
F.
Ulrich
Hartl
Department
of
Cellular
Biochemistry,
Max
Planck
Institute
Am
Klopferspitz
18,
82152
Martinsried,
Germany
Correspondence:
uhartl{at}biochem.mpg.de
Eukaryotes
have
evolved
various
quality
control
mechanisms
to
promote
proteostasis
in
the
endoplasmic
reticulum
(ER).
Selective
removal
of
certain
ER
domains
via
autophagy
(termed
as
ER-phagy)
has
emerged
a
major
mechanism.
However,
degree
which
ER-phagy
is
employed
by
other
branches
ER-quality
remains
largely
elusive.
Here,
we
identify
cytosolic
protein,
C53,
that
specifically
recruited
autophagosomes
during
ER-stress,
both
plant
and
mammalian
cells.
C53
interacts
with
ATG8
distinct
binding
epitope,
featuring
shuffled
interacting
motif
(sAIM).
senses
proteotoxic
stress
lumen
forming
tripartite
receptor
complex
ER-associated
ufmylation
ligase
UFL1
its
membrane
adaptor
DDRGK1.
The
C53/UFL1/DDRGK1
activated
stalled
ribosomes
induces
degradation
internal
or
passenger
proteins
ER.
Consistently,
mutants
are
highly
susceptible
stress.
Thus,
forms
an
ancient
pathway
bridges
selective
ribosome-associated
Experimental & Molecular Medicine,
Journal Year:
2021,
Volume and Issue:
53(2), P. 151 - 167
Published: Feb. 1, 2021
Abstract
The
endoplasmic
reticulum
(ER)
is
an
essential
organelle
of
eukaryotic
cells.
Its
main
functions
include
protein
synthesis,
proper
folding,
modification,
and
the
transportation
synthesized
proteins.
Any
perturbations
in
ER
function,
such
as
increased
demand
for
folding
or
accumulation
unfolded
misfolded
proteins
lumen,
lead
to
a
stress
response
called
(UPR).
primary
aim
UPR
restore
cellular
homeostasis;
however,
it
triggers
apoptotic
signaling
during
prolonged
stress.
core
mechanisms
response,
failure
respond
stress,
final
fate
cell
are
not
yet
clear.
Here,
we
discuss
cross
talk
between
mitochondria
its
significance,
conditions
that
can
trigger
failure.
We
also
describe
how
redox
environment
affects
vice
versa,
aftermath
integrating
discussion
on
imbalance-induced
progressing
death
dynamic
pathophysiological
changes.
Cold Spring Harbor Perspectives in Biology,
Journal Year:
2018,
Volume and Issue:
11(4), P. a033894 - a033894
Published: Nov. 5, 2018
Steffen
Preissler
and
David
Ron
Cambridge
Institute
for
Medical
Research,
University
of
Cambridge,
CB2
0XY,
United
Kingdom
Correspondence:
sp693{at}cam.ac.uk;
dr360{at}medschl.cam.ac.uk
