The interconnective role of the UPS and autophagy in the quality control of cancer mitochondria
Cellular and Molecular Life Sciences,
Год журнала:
2025,
Номер
82(1)
Опубликована: Янв. 12, 2025
Uncontrollable
cancer
cell
growth
is
characterized
by
the
maintenance
of
cellular
homeostasis
through
continuous
accumulation
misfolded
proteins
and
damaged
organelles.
This
review
delineates
roles
two
complementary
synergistic
degradation
systems,
ubiquitin–proteasome
system
(UPS)
autophagy-lysosome
system,
in
organelles
for
intracellular
recycling.
We
emphasize
interconnected
decision-making
processes
systems
maintaining
homeostasis,
such
as
biophysical
state
substrates,
receptor
oligomerization
potentials
(e.g.,
p62),
compartmentalization
capacities
membrane
structures).
Mitochondria,
hubs
respiration
metabolism,
are
implicated
tumorigenesis.
In
subsequent
sections,
we
thoroughly
examine
mechanisms
mitochondrial
quality
control
(MQC)
preserving
human
cells.
Notably,
explored
relationships
between
dynamics
(fusion
fission)
various
MQC
processes—including
UPS,
proteases,
mitophagy—in
context
repair
pathways.
Finally,
assessed
potential
targeting
(including
molecular
chaperones,
dynamics,
mitophagy
biogenesis)
therapeutic
strategies.
Understanding
underlying
may
offer
novel
insights
future
therapies.
highlights
UPS
degrading
proteins,
emphasizing
substrate
states,
oligomerization,
homeostasis.
Innovatively
links
coordination
to
examining
interplay
these
pathways
varying
degrees
damage.
Язык: Английский
ZLN005, a PGC-1α agonist, delays photoreceptor degeneration by enhancing mitochondrial biogenesis in a murine model of retinitis pigmentosa
Neuropharmacology,
Год журнала:
2025,
Номер
269, С. 110361 - 110361
Опубликована: Фев. 12, 2025
Retinitis
pigmentosa
(RP)
is
a
hereditary
neurodegenerative
disease
characterized
by
the
degeneration
of
photoreceptors
caused
mutations
in
various
genes.
Increasing
evidence
suggests
that
mitochondrial
biogenesis
plays
critical
role
many
diseases.
This
study
investigated
rd1
mice,
widely
recognized
model
RP.
Male
C57BL/6
mice
and
age-matched
were
used
for
vivo
experiments,
while
H2O2
was
employed
on
661w
cells
to
establish
an
vitro
model.
Our
findings
revealed
regulatory
PGC-1α/NRF-1/TFAM
pathway
significantly
downregulated
mice.
Treatment
with
ZLN005,
PGC-1α
agonist,
markedly
improved
visual
function
alleviated
thinning
retinal
outer
nuclear
layer.
Additionally,
ZLN005
enhanced
restored
photoreceptors.
Further
analysis
confirmed
rescued
photoreceptor
promoting
through
pathway.
In
summary,
our
results
highlight
progression
offers
potential
strategy
delay
RP
maintaining
could
be
combined
existing
therapies
improving
treatment
outcomes
synergistic
pathways.
Язык: Английский