Genes & Development,
Год журнала:
2015,
Номер
29(10), С. 989 - 999
Опубликована: Май 15, 2015
Two
Parkinson's
disease
(PD)-associated
proteins,
the
mitochondrial
kinase
PINK1
and
E3-ubiquitin
(Ub)
ligase
PARKIN,
are
central
to
quality
control.
In
this
pathway,
accumulates
on
defective
mitochondria,
eliciting
translocation
of
PARKIN
from
cytosol
mediate
clearance
damaged
mitochondria
via
autophagy
(mitophagy).
Throughout
different
stages
mitophagy,
post-translational
modifications
(PTMs)
critical
for
regulation
activity
function.
Indeed,
activation
recruitment
onto
involves
PINK1-mediated
phosphorylation
both
Ub.
Through
a
stepwise
cascade,
is
converted
an
autoinhibited
enzyme
into
active
phospho-Ub-dependent
E3
ligase.
Upon
activation,
ubiquitinates
itself
in
concert
with
many
substrates.
The
Ub
conjugates
attached
these
substrates
can
turn
be
phosphorylated
by
PINK1,
which
triggers
further
cycles
activation.
This
feed-forward
amplification
loop
regulates
mitophagy.
However,
precise
steps
sequence
PTMs
cascade
only
now
being
uncovered.
For
instance,
assembled
consist
predominantly
noncanonical
K6-linked
chains.
Moreover,
reversible
disassembled
deubiquitinating
enzymes
(DUBs),
including
Ub-specific
protease
8
(USP8),
USP15,
USP30.
impede
DUBs,
adding
new
layer
complexity
PARKIN-mediated
mitophagy
PTMs.
It
therefore
evident
that
insight
how
regulate
PINK1–PARKIN
pathway
will
our
understanding
Cell Research,
Год журнала:
2016,
Номер
26(4), С. 399 - 422
Опубликована: Март 25, 2016
Protein
ubiquitination
is
a
dynamic
multifaceted
post-translational
modification
involved
in
nearly
all
aspects
of
eukaryotic
biology.
Once
attached
to
substrate,
the
76-amino
acid
protein
ubiquitin
subjected
further
modifications,
creating
multitude
distinct
signals
with
cellular
outcomes,
referred
as
'ubiquitin
code'.
Ubiquitin
can
be
ubiquitinated
on
seven
lysine
(Lys)
residues
or
N-terminus,
leading
polyubiquitin
chains
that
encompass
complex
topologies.
Alternatively
addition,
Lys
modified
by
ubiquitin-like
molecules
(such
SUMO
NEDD8).
Finally,
also
acetylated
Lys,
phosphorylated
Ser,
Thr
Tyr
residues,
and
each
has
potential
dramatically
alter
signaling
outcome.
While
number
distinctly
species
cells
mind-boggling,
much
progress
been
made
characterize
roles
many
enzymes
receptors
have
identified
create,
recognize
remove
these
modifications.
We
here
provide
an
overview
various
modifications
present
cells,
highlight
recent
chain
then
discuss
findings
field
acetylation
phosphorylation,
focus
Ser65-phosphorylation
its
role
mitophagy
Parkin
activation.
Molecular Cell,
Год журнала:
2016,
Номер
61(5), С. 654 - 666
Опубликована: Март 1, 2016
A
decline
in
mitochondrial
quality
and
activity
has
been
associated
with
normal
aging
correlated
the
development
of
a
wide
range
age-related
diseases.
Here,
we
review
evidence
that
mitochondria
function
contributes
to
aging.
In
particular,
discuss
how
contribute
specific
aspects
process,
including
cellular
senescence,
chronic
inflammation,
age-dependent
stem
cell
activity.
Signaling
pathways
regulating
unfolded
protein
response
mitophagy
are
also
reviewed,
particular
emphasis
placed
on
these
might,
turn,
regulate
longevity.
Taken
together,
observations
suggest
influence
or
number
key
strategies
directed
at
improving
might
have
far-reaching
beneficial
effects.
Essays in Biochemistry,
Год журнала:
2018,
Номер
62(3), С. 341 - 360
Опубликована: Июль 20, 2018
Mitochondria
are
highly
dynamic
organelles
undergoing
coordinated
cycles
of
fission
and
fusion,
referred
as
‘mitochondrial
dynamics’,
in
order
to
maintain
their
shape,
distribution
size.
Their
transient
rapid
morphological
adaptations
crucial
for
many
cellular
processes
such
cell
cycle,
immunity,
apoptosis
mitochondrial
quality
control.
Mutations
the
core
machinery
components
defects
dynamics
have
been
associated
with
numerous
human
diseases.
These
transitions
mainly
ensured
by
large
GTPases
belonging
Dynamin
family.
Mitochondrial
is
a
multi-step
process
allowing
division
one
mitochondrion
two
daughter
mitochondria.
It
regulated
recruitment
GTPase
Dynamin-related
protein
1
(Drp1)
adaptors
at
actin-
endoplasmic
reticulum-mediated
constriction
sites.
Drp1
oligomerization
followed
leads
2
terminate
membrane
scission.
Inner
has
proposed
be
an
independent
calcium
influx.
fusion
driven
two-step
outer
mediated
mitofusins
inner
optic
atrophy
1.
In
addition
role
lipid
composition,
several
members
can
undergo
post-translational
modifications
modulating
these
processes.
Understanding
molecular
mechanisms
controlling
decipher
how
shape
meets
function
increase
knowledge
on
basis
diseases
morphology
defects.
This
article
will
describe
overview
that
govern
mammals.
Annual Review of Pathology Mechanisms of Disease,
Год журнала:
2019,
Номер
15(1), С. 235 - 259
Опубликована: Окт. 5, 2019
The
dynamic
properties
of
mitochondria-including
their
fusion,
fission,
and
degradation-are
critical
for
optimal
function
in
energy
generation.
interplay
fusion
fission
confers
widespread
benefits
on
mitochondria,
including
efficient
transport,
increased
homogenization
the
mitochondrial
population,
oxidative
phosphorylation.
These
arise
through
control
morphology,
content
exchange,
equitable
inheritance
maintenance
high-quality
DNA,
segregation
damaged
mitochondria
degradation.
key
components
machinery
mediating
belong
to
dynamin
family
GTPases
that
utilize
GTP
hydrolysis
drive
mechanical
work
biological
membranes.
Defects
this
cause
a
range
diseases
especially
affect
nervous
system.
In
addition,
several
common
diseases,
neurodegenerative
cancer,
strongly
dynamics.
The Journal of Cell Biology,
Год журнала:
2016,
Номер
212(4), С. 379 - 387
Опубликована: Фев. 8, 2016
Mitochondria
are
renowned
for
their
central
bioenergetic
role
in
eukaryotic
cells,
where
they
act
as
powerhouses
to
generate
adenosine
triphosphate
from
oxidation
of
nutrients.
At
the
same
time,
these
organelles
highly
dynamic
and
undergo
fusion,
fission,
transport,
degradation.
Each
processes
is
critical
maintaining
a
healthy
mitochondrial
population.
Given
metabolic
function
mitochondria,
it
not
surprising
that
dynamics
bioenergetics
reciprocally
influence
each
other.
We
review
properties
with
an
emphasis
on
how
respond
cellular
signaling
events
affect
metabolism.
Mitochondrial
apoptosis
is
mediated
by
BAK
and
BAX,
two
proteins
that
induce
mitochondrial
outer
membrane
permeabilization,
leading
to
cytochrome
c
release
activation
of
apoptotic
caspases.
In
the
absence
active
caspases,
DNA
(mtDNA)
triggers
innate
immune
cGAS/STING
pathway,
causing
dying
cells
secrete
type
I
interferon.
How
cGAS
gains
access
mtDNA
remains
unclear.
We
used
live-cell
lattice
light-sheet
microscopy
examine
network
in
mouse
embryonic
fibroblasts.
found
after
BAK/BAX
loss,
broke
down
large
pores
appeared
membrane.
These
macropores
allowed
inner
herniate
into
cytosol,
carrying
with
it
matrix
components,
including
genome.
Apoptotic
caspases
did
not
prevent
herniation
but
dismantled
cell
suppress
mtDNA-induced
signaling.
