Journal of Inherited Metabolic Disease,
Journal Year:
2024,
Volume and Issue:
48(1)
Published: June 14, 2024
Abstract
Mitochondria
are
dynamic
cellular
organelles
with
complex
roles
in
metabolism
and
signalling.
Primary
mitochondrial
disorders
a
group
of
approximately
400
monogenic
arising
from
pathogenic
genetic
variants
impacting
structure,
ultrastructure
and/or
function.
Amongst
these
disorders,
defects
lipid
biosynthesis,
especially
the
unique
membrane
cardiolipin,
biology
an
emerging
characterised
by
clinical
heterogeneity,
but
recurrent
features
including
cardiomyopathy,
encephalopathy,
neurodegeneration,
neuropathy
3‐methylglutaconic
aciduria.
This
review
discusses
synthesis
membrane,
contact
site
cristae
organising
system
(MICOS),
dynamics
trafficking,
associated
each
processes.
We
highlight
overlapping
functions
proteins
involved
biosynthesis
protein
import
into
mitochondria,
pointing
to
overarching
coordination
synchronisation
functions.
also
focuses
on
interactions
between
mitochondria
other
organelles,
namely
endoplasmic
reticulum,
peroxisomes,
lysosomes
droplets.
signpost
that
may
explain
observation
secondary
dysfunction
heterogeneous
pathological
Disruption
organellar
ultimately
impairs
homeostasis
organismal
health,
highlighting
central
role
human
health
disease.
Nature Communications,
Journal Year:
2023,
Volume and Issue:
14(1)
Published: May 24, 2023
Abstract
Phospholipase
D3
(PLD3)
polymorphisms
are
linked
to
late-onset
Alzheimer’s
disease
(LOAD).
Being
a
lysosomal
5’-3’
exonuclease,
its
neuronal
substrates
remained
unknown
as
well
how
defective
nucleotide
catabolism
connects
AD-proteinopathy.
We
identified
mitochondrial
DNA
(mtDNA)
major
physiological
substrate
and
show
manifest
build-up
in
lysosomes
of
PLD3-defective
cells.
mtDNA
accretion
creates
degradative
(proteolytic)
bottleneck
that
presents
at
the
ultrastructural
level
marked
abundance
multilamellar
bodies,
often
containing
remnants,
which
correlates
with
increased
PINK1-dependent
mitophagy.
Lysosomal
leakage
cytosol
activates
cGAS–STING
signaling
upregulates
autophagy
induces
amyloid
precursor
C-terminal
fragment
(APP-CTF)
cholesterol
accumulation.
STING
inhibition
largely
normalizes
APP-CTF
levels,
whereas
an
APP
knockout
PLD3-deficient
backgrounds
lowers
activation
biosynthesis.
Collectively,
we
demonstrate
molecular
cross-talks
through
feedforward
loops
between
turnover,
cGAS-STING
metabolism
that,
when
dysregulated,
result
endolysosomal
demise
observed
LOAD.
Science Advances,
Journal Year:
2023,
Volume and Issue:
9(29)
Published: July 19, 2023
Mutations
in
the
E3
ubiquitin
ligase
parkin
are
most
common
cause
of
early-onset
Parkinson's
disease
(PD).
Although
modulates
mitochondrial
and
endolysosomal
homeostasis
during
cellular
stress,
whether
regulates
lysosomal
cross-talk
under
physiologic
conditions
remains
unresolved.
Using
transcriptomics,
metabolomics
super-resolution
microscopy,
we
identify
amino
acid
metabolism
as
a
disrupted
pathway
iPSC-derived
dopaminergic
neurons
from
patients
with
PD.
Compared
to
isogenic
controls,
mutant
exhibit
decreased
mitochondria-lysosome
contacts
via
destabilization
active
Rab7.
Subcellular
reveals
accumulation
lysosomes
their
deficiency
mitochondria.
Knockdown
Rab7
GTPase-activating
protein
TBC1D15
restores
tethering
ameliorates
subcellular
profiles
neurons.
Our
data
thus
uncover
function
promoting
through
stabilization
suggest
that
modulation
interorganelle
may
serve
potential
target
for
ameliorating
dyshomeostasis
disease.
Neurobiology of Disease,
Journal Year:
2022,
Volume and Issue:
170, P. 105753 - 105753
Published: May 13, 2022
Under
physiological
conditions
in
vivo
astrocytes
internalize
and
degrade
neuronal
mitochondria
a
process
called
transmitophagy.
Mitophagy
is
widely
reported
to
be
impaired
neurodegeneration
but
it
unknown
whether
how
transmitophagy
altered
Alzheimer's
disease
(AD).
Here
we
report
that
the
internalization
of
significantly
increased
isolated
from
AD
mouse
brains.
We
also
demonstrate
degradation
by
mice
at
age
6
months
onwards.
Furthermore,
for
first
time
similar
phenomenon
between
human
neurons
astrocytes,
murine
hippocampi
vivo.
The
results
suggest
involvement
S100a4
mitochondrial
transfer
together
with
significant
increases
mitophagy
regulator
reactive
oxygen
species
aged
astrocytes.
These
findings
neuron-supporting
functions
provide
starting
point
studying
molecular
mechanisms
AD.
Chemical Society Reviews,
Journal Year:
2022,
Volume and Issue:
52(3), P. 942 - 972
Published: Dec. 14, 2022
Mitochondria
are
inextricably
linked
to
the
development
of
diseases
and
cell
metabolism
disorders.
Super-resolution
imaging
(SRI)
is
crucial
in
enhancing
our
understanding
mitochondrial
ultrafine
structures
functions.
In
addition
high-precision
instruments,
super-resolution
microscopy
relies
heavily
on
fluorescent
materials
with
unique
photophysical
properties.
Small-molecule
fluorogenic
probes
(SMFPs)
have
excellent
properties
that
make
them
ideal
for
SRI.
This
paper
summarizes
recent
advances
field
SMFPs,
a
focus
chemical
spectroscopic
required
Finally,
we
discuss
future
challenges
this
field,
including
design
principles
SMFPs
nanoscopic
techniques.
Nano Letters,
Journal Year:
2023,
Volume and Issue:
23(10), P. 4660 - 4668
Published: May 8, 2023
Oxidative
stress
is
known
to
be
the
cause
of
several
neurovascular
diseases,
including
neurodegenerative
disorders,
since
increase
reactive
oxygen
species
(ROS)
levels
can
lead
cellular
damage,
blood-brain
barrier
leaking,
and
inflammatory
pathways.
Herein,
we
demonstrate
therapeutic
potential
5
nm
platinum
nanoparticles
(PtNPs)
effectively
scavenge
ROS
in
different
models
unit.
We
investigated
mechanism
underlying
PtNP
biological
activities,
analyzing
influence
evolving
environment
during
particle
trafficking
disclosing
a
key
role
protein
corona,
which
elicited
an
effective
switch-off
catalytic
properties,
promoting
their
selective
The Journal of Cell Biology,
Journal Year:
2024,
Volume and Issue:
223(5)
Published: Feb. 15, 2024
Loss-of-function
mutations
in
VPS13C
are
linked
to
early-onset
Parkinson’s
disease
(PD).
While
has
been
previously
studied
non-neuronal
cells,
the
neuronal
role
of
disease-relevant
human
dopaminergic
neurons
not
elucidated.
Using
live-cell
microscopy,
we
investigated
regulating
lysosomal
dynamics
and
function
iPSC-derived
neurons.
Loss
disrupts
morphology
with
increased
inter-lysosomal
contacts,
leading
impaired
motility
cellular
distribution,
as
well
defective
hydrolytic
activity
acidification.
We
identified
Rab10
a
phospho-dependent
interactor
on
lysosomes
observed
decreased
phospho-Rab10-mediated
stress
response
upon
loss
VPS13C.
These
findings
highlight
an
important
homeostasis
suggest
that
disruptions
Rab10-mediated
contribute
pathogenesis
VPS13C-linked
PD.
The Journal of Cell Biology,
Journal Year:
2024,
Volume and Issue:
223(9)
Published: Aug. 12, 2024
Most
secreted
proteins
are
transported
through
the
“conventional”
endoplasmic
reticulum–Golgi
apparatus
exocytic
route
for
their
delivery
to
cell
surface
and
release
into
extracellular
space.
Nonetheless,
formative
discoveries
have
underscored
existence
of
alternative
or
“unconventional”
secretory
routes,
which
play
a
crucial
role
in
exporting
diverse
array
cytosolic
outside
response
intrinsic
demands,
external
cues,
environmental
changes.
In
this
context,
lysosomes
emerge
as
dynamic
organelles
positioned
at
crossroads
multiple
intracellular
trafficking
pathways,
endowed
with
capacity
fuse
plasma
membrane
recognized
key
both
conventional
unconventional
protein
secretion.
The
recent
recognition
lysosomal
transport
exocytosis
secretion
cargo
provides
new
promising
insights
our
understanding
numerous
physiological
processes.
