G3 Genes Genomes Genetics,
Год журнала:
2024,
Номер
14(9)
Опубликована: Июнь 26, 2024
Abstract
Multicopied
mitogenome
are
prone
to
mutation
during
replication
often
resulting
in
heteroplasmy.
The
derived
variants
a
cell,
organ,
or
an
individual
animal
constitute
mitogene
pool.
pool
is
initiated
by
small
fraction
of
the
egg
However,
characteristics
and
relationship
between
them
has
not
yet
been
investigated.
This
study
quantitatively
analyzed
heteroplasmy
landscape,
genetic
loads,
selection
strength
hatchling
silver
carp
(Hypophthalmichthys
molitrix)
using
high-throughput
resequencing.
results
showed
heteroplasmic
sites
distribute
across
whole
both
eggs
hatchlings.
dominant
substitution
was
Transversion
Transition
hatching
accounting
for
95.23%±2.07%
85.38%±6.94%
total
HP
sites,
respectively.
loads
were
0.293±0.044
0.228±0.022
hatchlings
(P=0.048).
dN/dS
ratio
58.03±38.98
9.44±3.93
(P=0.037).
These
suggest
that
mitogenomes
under
strong
positive
with
tolerance
deleterious
effects,
while
but
much
weaker
showing
marked
quality
control.
Based
on
these
findings,
we
proposed
trans-generation
dynamics
model
explain
differential
development
mode
two
oocyte
maturation
ontogenesis
offspring.
sheds
light
significance
persistence
populations
subsequent
integration
ecological
studies
conservation
practices.
Molecular Cell,
Год журнала:
2023,
Номер
83(19), С. 3404 - 3420
Опубликована: Окт. 1, 2023
Mitochondria
are
central
hubs
of
cellular
metabolism
that
also
play
key
roles
in
signaling
and
disease.
It
is
therefore
fundamentally
important
mitochondrial
quality
activity
tightly
regulated.
Mitochondrial
degradation
pathways
contribute
to
control
networks
can
regulate
the
metabolic
profile
mitochondria
ensure
homeostasis.
Here,
we
cover
many
varied
ways
which
cells
degrade
or
remove
their
unwanted
mitochondria,
ranging
from
mitophagy
extrusion.
The
molecular
signals
driving
these
discussed,
including
physiological
contexts
under
different
engaged.
Frontiers in Endocrinology,
Год журнала:
2024,
Номер
15
Опубликована: Апрель 17, 2024
Mitochondria
plays
an
essential
role
in
regulating
cellular
metabolic
homeostasis,
proliferation/differentiation,
and
cell
death.
Mitochondrial
dysfunction
is
implicated
many
age-related
pathologies.
Evidence
supports
that
the
of
mitochondria
decline
mitochondrial
DNA
copy
number
negatively
affect
ovarian
aging.
However,
mechanism
aging
still
unclear.
Treatment
methods,
including
antioxidant
applications,
transplantation,
emerging
biomaterials,
advanced
technologies,
are
being
used
to
improve
function
restore
oocyte
quality.
This
article
reviews
key
evidence
research
updates
on
damage
pathogenesis
aging,
emphasizing
may
accelerate
lead
senescence
as
well
exploring
potential
methods
for
using
mechanisms
slow
down
Abstract
Mitochondrial
DNA
(mtDNA)
diseases
are
multi‐systemic
disorders
caused
by
mutations
affecting
a
fraction
or
the
entirety
of
mtDNA
copies.
Currently,
there
no
approved
therapies
for
majority
diseases.
Challenges
associated
with
engineering
have
in
fact
hindered
study
defects.
Despite
these
difficulties,
it
has
been
possible
to
develop
valuable
cellular
and
animal
models
Here,
we
describe
recent
advances
base
editing
generation
three‐dimensional
organoids
from
patient‐derived
human‐induced
pluripotent
stem
cells
(iPSCs).
Together
already
available
modeling
tools,
combination
novel
technologies
could
allow
determining
impact
specific
distinct
human
cell
types
might
help
uncover
how
mutation
load
segregates
during
tissue
organization.
iPSC‐derived
also
represent
platform
identification
treatment
strategies
probing
vitro
effectiveness
gene
therapies.
These
studies
potential
increase
our
mechanistic
understanding
may
open
way
highly
needed
personalized
therapeutic
interventions.
Nature Communications,
Год журнала:
2024,
Номер
15(1)
Опубликована: Фев. 10, 2024
Abstract
Mitochondria
are
inherited
exclusively
from
the
mothers
and
required
for
proper
development
of
embryos.
Hence,
germline
mitochondrial
quality
is
highly
regulated
during
oogenesis
to
ensure
oocyte
viability.
How
nutrient
availability
influences
control
unclear.
Here
we
find
that
fasting
leads
accumulation
clumps
arrest
in
Drosophila
.
Fasting
induces
downregulation
DIP1-Clueless
pathway,
leading
an
increase
expression
a
stable
intronic
sequence
RNA
called
sisR-1
Mechanistically,
localizes
inhibit
poly-ubiquitination
outer
protein
Porin/VDAC1,
thereby
suppressing
p62-mediated
mitophagy.
Alleviation
fasting-induced
high
levels
by
either
RNAi
or
refeeding
mitophagy,
resumption
improvement
quality.
Thus,
our
study
provides
possible
mechanism
which
can
improve
modulating
pathway.
Of
note,
uncover
response
also
regulates
clumping
deprivation,
heat
shock
aging,
suggesting
broader
role
this
control.
Trends in Pharmacological Sciences,
Год журнала:
2024,
Номер
45(3), С. 225 - 242
Опубликована: Фев. 23, 2024
High
levels
of
pathogenic
mitochondrial
DNA
(mtDNA)
variants
lead
to
severe
genetic
diseases,
and
the
accumulation
such
mutants
may
also
contribute
common
disorders.
Thus,
selecting
against
these
is
a
major
goal
in
medicine.
Although
mutant
mtDNA
can
drift
randomly,
mounting
evidence
indicates
that
active
forces
play
role
selection
for
variants.
The
underlying
mechanisms
are
beginning
be
clarified,
recent
studies
suggest
metabolic
cues,
including
fuel
availability,
shaping
heteroplasmy.
In
context
pathological
mtDNAs,
remodeling
nutrient
metabolism
supports
mitochondria
with
deleterious
mtDNAs
enables
them
outcompete
functional
owing
replicative
advantage.
elevated
requirement
represents
Achilles'
heel
because
small
molecules
restrict
consumption
or
interfere
sensing
purge
cells
restore
respiration.
These
advances
herald
dawn
new
era
small-molecule
therapies
counteract
mtDNAs.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 3, 2025
Abstract
The
quality
of
inherited
mitochondria
determines
embryonic
viability
1
,
metabolic
health
during
adulthood
and
future
generation
endurance.
oocyte
is
the
source
all
zygotic
2
mitochondrial
under
strict
developmental
regulation
early
oogenesis
3–5
.
Yet,
fully
developed
oocytes
exhibit
presence
deleterious
DNA
(mtDNA)
6,7
dysfunction
from
high
levels
endogenous
reactive
oxygen
species
8
exogenous
toxicants
9
How
prevent
transmission
damaged
to
zygotes
unknown.
Here
we
discover
that
onset
oocyte-to-zygote
transition
(OZT)
developmentally
triggers
a
robust
rapid
mitophagy
event
term
at
OZT
(MOZT).
We
show
MOZT
requires
fragmentation,
activation
macroautophagy
system
receptor
FUNDC1,
but
not
prevalent
factors
PINK1
BNIP3.
Oocytes
upregulate
expression
FUNDC1
in
response
diverse
insults,
including
mtDNA
mutations
damage,
uncoupling
stress,
dysfunction,
thereby
promoting
selection
against
mitochondria.
Loss
leads
increased
inheritance
impaired
bioenergetic
progeny,
resulting
diminished
extinction
descendent
populations.
Our
findings
reveal
FUNDC1-mediated
as
mechanism
preserves
mother-to-offspring
promotes
continuity.
These
results
may
explain
how
mature
many
harboring
mutant
give
rise
healthy
embryos
with
reduced
mtDNA.
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
