TRPML1 activation ameliorates lysosomal phenotypes in CLN3 deficient retinal pigment epithelial cells
Daniela Wünkhaus,
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R. Tang,
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Kwamina Nyame
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et al.
Scientific Reports,
Journal Year:
2024,
Volume and Issue:
14(1)
Published: July 29, 2024
Mutations
in
the
lysosomal
membrane
protein
CLN3
cause
Juvenile
Neuronal
Ceroid
Lipofuscinosis
(JNCL).
Activation
of
ion
channel
TRPML1
has
previously
been
shown
to
be
beneficial
several
neurodegenerative
disease
models.
Here,
we
tested
whether
activation
rescues
disease-associated
phenotypes
CLN3-deficient
retinal
pigment
epithelial
(ARPE-19
CLN3-KO)
cells.
ARPE-19
CLN3-KO
cells
accumulate
LAMP1
positive
organelles
and
show
storage
mitochondrial
ATPase
subunit
C
(SubC),
globotriaosylceramide
(Gb3),
glycerophosphodiesters
(GPDs),
whereas
bis(monoacylglycero)phosphate
(BMP/LBPA)
lipid
levels
were
significantly
decreased.
reduced
Gb3
SubC
but
failed
restore
BMP
TRPML1-mediated
decrease
was
TFEB-independent,
identified
enhanced
exocytosis
as
a
likely
mechanism
for
clearing
including
GPDs.
Therefore,
represent
human
cell
model
showing
many
described
core
deficits,
some
which
can
improved
using
agonists.
Language: Английский
Mechanisms and functions of lysosomal lipid homeostasis
Cell chemical biology,
Journal Year:
2025,
Volume and Issue:
unknown
Published: March 1, 2025
Language: Английский
Lack of significant ganglioside changes in Slc17a5 heterozygous mice: Relevance to FSASD and Parkinson's disease
Marya S. Sabir,
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Mahin Hossain,
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Laura Pollard
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et al.
Biochemistry and Biophysics Reports,
Journal Year:
2025,
Volume and Issue:
42, P. 101979 - 101979
Published: March 14, 2025
Language: Английский
Mitochondria-organelle crosstalk in establishing compartmentalized metabolic homeostasis
Molecular Cell,
Journal Year:
2025,
Volume and Issue:
85(8), P. 1487 - 1508
Published: April 1, 2025
Language: Английский
Global organelle profiling reveals subcellular localization and remodeling at proteome scale
Cell,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Dec. 1, 2024
Defining
the
subcellular
distribution
of
all
human
proteins
and
their
remodeling
across
cellular
states
remains
a
central
goal
in
cell
biology.
Here,
we
present
high-resolution
strategy
to
map
organization
using
organelle
immunocapture
coupled
mass
spectrometry.
We
apply
this
workflow
cell-wide
collection
membranous
membraneless
compartments.
A
graph-based
analysis
assigns
localization
over
7,600
proteins,
defines
spatial
networks,
uncovers
interconnections
between
Our
approach
can
be
deployed
comprehensively
profile
proteome
during
perturbation.
By
characterizing
landscape
following
HCoV-OC43
viral
infection,
discover
that
many
are
regulated
by
changes
rather
than
abundance.
results
establish
proteome-wide
provides
key
insights
for
elucidating
responses,
uncovering
an
essential
role
ferroptosis
OC43
infection.
dataset
explored
at
organelles.czbiohub.org.
Language: Английский