TRAF6 integrates innate immune signals to regulate glucose homeostasis via Parkin-dependent and -independent mitophagy
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 1, 2025
ABSTRACT
Activation
of
innate
immune
signaling
occurs
during
the
progression
immunometabolic
diseases,
including
type
2
diabetes
(T2D),
yet
impact
on
glucose
homeostasis
is
controversial.
Here,
we
report
that
E3
ubiquitin
ligase
TRAF6
integrates
signals
following
diet-induced
obesity
to
promote
through
induction
mitophagy.
Whereas
was
dispensable
for
and
pancreatic
β-cell
function
under
basal
conditions,
pivotal
insulin
secretion,
mitochondrial
respiration,
increases
in
mitophagy
metabolic
stress
both
mouse
human
islets.
Indeed,
critical
recruitment
machinery
within
ubiquitin-mediated
(Parkin-dependent)
receptor-mediated
(Parkin-independent)
pathways
upon
stress.
Intriguingly,
effect
deficiency
fully
reversed
by
concomitant
Parkin
deficiency.
Thus,
our
results
implicate
a
role
cross-regulation
ubiquitin-
receptor-
mediated
restriction
Parkin.
Together,
illustrate
β-cells
engage
adaptively
respond
diabetogenic
environment.
Язык: Английский
Transcriptional Dynamics Uncover the Role of BNIP3 in Mitophagy during Muscle Remodeling in Drosophila
Опубликована: Март 12, 2025
Differentiated
muscle
cells
contain
myofibrils
and
well-organized
organelles,
enabling
powerful
contractions.
Muscle
cell
reorganization
occurs
in
response
to
various
physiological
stimuli;
however,
the
mechanisms
behind
this
remodeling
remain
enigmatic
due
lack
of
a
genetically
trackable
system.
Previously,
we
reported
that
subset
larval
is
remodeled
into
adult
abdominal
through
an
autophagy-dependent
mechanism
Drosophila
.
To
unveil
underlying
remodeling,
performed
comparative
time-course
RNA-seq
analysis
isolated
with
or
without
autophagy.
It
revealed
both
transcriptional
dynamics
independent
autophagy
highlighted
significance
BNIP3-mediated
mitophagy
remodeling.
Mechanistically,
found
BNIP3
recruits
autophagic
machinery
mitochondria
its
LC3-interacting
(LIR)
motif
minimal
essential
region
(MER),
which
interact
Atg8a
Atg18a,
respectively.
Loss
leads
substantial
accumulation
mitochondria,
ultimately
impairing
In
summary,
study
demonstrates
BNIP3-dependent
critical
for
orchestrating
dynamic
process
Язык: Английский
Transcriptional Dynamics Uncover the Role of BNIP3 in Mitophagy during Muscle Remodeling in Drosophila
Опубликована: Март 12, 2025
Differentiated
muscle
cells
contain
myofibrils
and
well-organized
organelles,
enabling
powerful
contractions.
Muscle
cell
reorganization
occurs
in
response
to
various
physiological
stimuli;
however,
the
mechanisms
behind
this
remodeling
remain
enigmatic
due
lack
of
a
genetically
trackable
system.
Previously,
we
reported
that
subset
larval
is
remodeled
into
adult
abdominal
through
an
autophagy-dependent
mechanism
Drosophila
.
To
unveil
underlying
remodeling,
performed
comparative
time-course
RNA-seq
analysis
isolated
with
or
without
autophagy.
It
revealed
both
transcriptional
dynamics
independent
autophagy
highlighted
significance
BNIP3-mediated
mitophagy
remodeling.
Mechanistically,
found
BNIP3
recruits
autophagic
machinery
mitochondria
its
LC3-interacting
(LIR)
motif
minimal
essential
region
(MER),
which
interact
Atg8a
Atg18a,
respectively.
Loss
leads
substantial
accumulation
mitochondria,
ultimately
impairing
In
summary,
study
demonstrates
BNIP3-dependent
critical
for
orchestrating
dynamic
process
Язык: Английский
Molecular and epigenetic responses to crowding stress in rainbow trout (Oncorhynchus mykiss) skeletal muscle
Frontiers in Endocrinology,
Год журнала:
2025,
Номер
16
Опубликована: Апрель 16, 2025
Chronic
stress
is
a
critical
challenge
in
fish
aquaculture,
adversely
affecting
growth,
health,
and
overall
productivity.
Among
the
most
significant
chronic
stressors
intensive
farming
crowding,
which
triggers
release
of
cortisol,
primary
hormone
fish.
Cortisol
re-allocates
energy
away
from
growth-related
processes
toward
response
mechanisms.
Consequently,
overcrowded
often
exhibit
slower
growth
rates,
impaired
skeletal
muscle
development.
Understanding
mechanisms
underlying
crowding
their
long-term
effects,
including
epigenetic
changes,
essential
for
optimizing
conditions,
enhancing
welfare.
This
study
aims
to
characterize
physiological,
transcriptomic,
epigenomic
responses
juvenile
rainbow
trout
(Oncorhynchus
mykiss)
exposed
30
days
high
stocking
densities.
Crowding
led
decreased
weight
high-density
(HD)
group.
It
also
resulted
elevated
cortisol
levels,
oxidative
DNA
damage,
protein
carbonylation
muscle.
Using
RNA-seq,
we
identified
4,050
differentially
expressed
genes
(DEGs),
through
whole-genome
bisulfite
sequencing
(WGBS),
detected
11,672
methylated
(DMGs).
Integrative
analyses
revealed
263
with
negative
correlation
between
upregulated
expression
downregulated
methylation,
primarily
associated
autophagy,
mitophagy,
insulin
signaling
pathway.
Conversely,
299
exhibited
reverse
trend,
mainly
linked
ATP-dependent
chromatin
remodeling.
offers
first
detailed
exploration
molecular
stress,
integrating
RNA-seq
WGBS
analysis
trout,
offering
valuable
information
improving
aquaculture
practices.
Язык: Английский
Mitochondria‐Nuclear Crosstalk: Orchestrating mtDNA Maintenance
Environmental and Molecular Mutagenesis,
Год журнала:
2025,
Номер
unknown
Опубликована: Май 26, 2025
ABSTRACT
The
mitochondria
(mt)
and
nucleus
engage
in
a
dynamic
bidirectional
communication
to
maintain
cellular
homeostasis,
regulating
energy
production,
stress
response,
cell
fate.
Anterograde
signaling
directs
mt
function,
while
retrograde
conveys
metabolic
stress‐related
changes
from
the
nucleus.
Central
this
crosstalk
is
mitochondrial
DNA
(mtDNA),
which
encodes
key
oxidative
phosphorylation
components.
MtDNA
integrity
preserved
through
quality
control
mechanisms,
including
fusion
fission
dynamics,
mitophagy,
nuclear‐encoded
repair.
Disruption
these
pathways
contributes
dysfunction,
stress,
genetic
instability—hallmarks
of
aging
diseases.
Additionally,
redox
NAD+
homeostasis
integrate
nuclear
responses,
modulating
transcriptional
programs
that
support
biogenesis
adaptation.
This
review
explores
molecular
mechanisms
coordinating
mito‐nuclear
interactions,
emphasizing
their
role
maintaining
mtDNA
equilibrium.
Understanding
processes
provides
insights
into
how
dysfunction
drives
disease,
paving
way
for
targeted
therapeutic
strategies.
Язык: Английский
Autophagy and Mitophagy in Cancer Metabolic Remodeling
IGI Global eBooks,
Год журнала:
2025,
Номер
unknown, С. 21 - 70
Опубликована: Июнь 5, 2025
Autophagy
and
mitophagy
are
vital
for
cellular
homeostasis,
especially
in
cancer
metabolic
remodeling,
where
they
play
complex
roles
both
tumor
suppression
promotion.
Autophagy,
a
recycling
mechanism,
helps
cells
survive
by
nutrients
generating
energy,
influencing
pathways
like
glycolysis
oxidative
phosphorylation,
essential
proliferation.
Mitophagy,
the
selective
degradation
of
mitochondria,
ensures
mitochondrial
quality,
maintaining
energy
regulating
ROS
levels,
aiding
adaptation
to
hypoxic,
nutrient-deprived
conditions.
The
chapter
also
examines
therapeutic
potential
targeting
autophagy
cancer.
While
these
processes
can
contribute
resistance
against
chemotherapy
radiotherapy,
emerging
strategies
aim
modulate
them
improved
treatment
outcomes.
Case
studies
clinical
trials
offer
insights
into
current
therapies,
highlighting
successes
challenges.
Ongoing
research
personalized
medicine
approaches
promising
avenues
innovative
treatments.
Язык: Английский
Development of Mitophagy Modulators and Inhibitors of Defective Mitophagy
IGI Global eBooks,
Год журнала:
2025,
Номер
unknown, С. 179 - 210
Опубликована: Июнь 5, 2025
Mitophagy,
a
selective
form
of
autophagy,
is
vital
for
maintaining
cellular
health
by
removing
dysfunctional
mitochondria.
This
process,
triggered
the
weakening
inner
mitochondrial
membrane,
crucial
in
highly
differentiated,
non-dividing
cells
like
neurons,
muscle
cells,
and
liver
cells.
A
balance
mitophagy
essential;
both
insufficient
excessive
activity
are
linked
to
age-related
disorders
such
as
neurodegenerative
diseases,
metabolic
issues,
heart
damage.
Computational
tools,
or
in-silico
methods,
have
become
powerful
predicting
biological
chemical
compounds,
assessing
their
potential
drug
candidates.
These
methods
particularly
useful
analyzing
natural
products,
which
offer
diverse
structures
development.
chapter
highlights
significance
mitophagy,
its
regulatory
pathways,
use
computational
techniques,
including
virtual
screening
molecular
docking,
identifying
regulators,
especially
from
product
libraries.
Язык: Английский
Mitophagy in Doxorubicin-Induced Cardiotoxicity: Insights into Molecular Biology and Novel Therapeutic Strategies
Biomolecules,
Год журнала:
2024,
Номер
14(12), С. 1614 - 1614
Опубликована: Дек. 17, 2024
Doxorubicin
is
a
chemotherapeutic
drug
utilized
for
solid
tumors
and
hematologic
malignancies,
but
its
clinical
application
hampered
by
life-threatening
cardiotoxicity,
including
cardiac
dilation
heart
failure.
Mitophagy,
cargo-specific
form
of
autophagy,
specifically
used
to
eliminate
damaged
mitochondria
in
autophagosomes
through
hydrolytic
degradation
following
fusion
with
lysosomes.
Recent
advances
have
unveiled
major
role
defective
mitophagy
the
etiology
DOX-induced
cardiotoxicity.
Moreover,
specific
interventions
targeting
this
mechanism
preserve
mitochondrial
function
emerged
as
potential
therapeutic
strategies
attenuate
However,
translation
challenging
because
unclear
mechanisms
action
pharmacological
adverse
effects.
This
review
aims
offer
fresh
perspectives
on
development
cardiotoxicity
investigate
that
focus
improve
management.
Язык: Английский