PLoS Pathogens,
Journal Year:
2024,
Volume and Issue:
20(12), P. e1012635 - e1012635
Published: Dec. 2, 2024
The
parasitic
protozoan
Trypanosoma
brucei
has
a
single
unit
mitochondrial
genome
linked
to
the
basal
body
of
flagellum
via
tripartite
attachment
complex
(TAC).
TAC
is
crucial
for
segregation
during
cytokinesis.
At
core
TAC,
outer
membrane
protein
TAC60
binds
inner
p166,
forming
permanent
contact
site
between
two
membranes.
Although
sites
membranes
are
common
and
serve
various
functions,
their
molecular
architecture
remains
largely
unknown.
This
study
elucidates
interaction
interface
TAC60-p166
site.
Using
in
silico
,
vitro
mutational
vivo
analyses,
we
identified
minimal
binding
segments
p166.
p166
consists
short
kinked
α-helix
that
interacts
with
C-terminal
Despite
presence
conserved
charged
residues
either
protein,
electrostatic
interactions
not
necessary
formation.
Instead,
driven
by
hydrophobic
effect,
as
converting
hydrophilic
amino
acids
disrupts
Current Research in Food Science,
Journal Year:
2025,
Volume and Issue:
10, P. 100972 - 100972
Published: Jan. 1, 2025
Resveratrol
(RES),
a
natural
polyphenolic
compound,
has
shown
promise
in
enhancing
skeletal
muscle
regeneration
and
metabolic
function.
This
study
aims
to
explore
the
impact
of
RES
on
after
injury
through
regulation
antioxidant
capacity
mitochondrial
biogenesis.
treatment
significantly
increased
ratio
tibialis
anterior
mass
body
weight,
alongside
reduced
fasting
glucose
levels.
Following
cardiotoxin-induced
injury,
improved
regeneration,
characterized
by
greater
formation
new
fibers
better
structural
repair
compared
control.
Notably,
gene
expression
analyses
demonstrated
that
RES-treated
mice
exhibited
elevated
levels
myogenic
markers,
such
as
paired
box
7
(Pax7),
factor
5
(Myf5),
myoblast
determination
protein
(MyoD),
Myogenin
(MyoG).
Concurrently,
yes-associated
(YAP)
increased,
underscoring
its
role
regulating
satellite
cell
activity.
Transcriptomic
analysis
identified
enriched
pathways
related
biogenesis,
with
transcription
factors
higher
DNA
content
mice.
Furthermore,
enhanced
via
Kelch-like
ECH-associated
1
(KEAP-1)/nuclear
erythroid
2-related
2
(NRF2)/heme
oxygenase-1
(HO-1)
signaling
pathway,
indicated
activities
total
capacity,
Glutathione
peroxidase
(GSH-PX),
superoxidase
dismutase
(SOD).
Collectively,
these
findings
suggest
not
only
promotes
but
also
supports
function
defenses,
positioning
it
food-derived
pharmaceutical
for
targeting
injury.
Nucleic Acids Research,
Journal Year:
2024,
Volume and Issue:
52(18), P. 11266 - 11282
Published: Aug. 1, 2024
Abstract
In
mammals,
the
leucine-rich
pentatricopeptide
repeat
protein
(LRPPRC)
and
stem-loop
interacting
RNA-binding
(SLIRP)
form
a
complex
in
mitochondrial
matrix
that
is
required
throughout
life
cycle
of
most
mRNAs.
Although
pathogenic
mutations
LRPPRC
SLIRP
genes
cause
devastating
human
diseases,
vivo
function
corresponding
proteins
incompletely
understood.
We
show
here
loss
mice
causes
decrease
I
levels
whereas
other
OXPHOS
complexes
are
unaffected.
generated
knock-in
to
study
interdependency
by
mutating
specific
amino
acids
necessary
for
formation.
When
formation
disrupted,
partially
degraded
disappears.
Livers
from
Lrpprc
had
impaired
translation
except
marked
increase
synthesis
ATP8.
Furthermore,
introduction
heteroplasmic
mtDNA
mutation
(m.C5024T
tRNAAla
gene)
into
Slirp
knockout
an
additive
effect
on
leading
embryonic
lethality
reduced
growth
mouse
fibroblasts.
To
summarize,
we
report
LRPPRC/SLIRP
critical
maintaining
normal
it
also
coordinates
tissue-specific
manner.
The Journal of Biochemistry,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Feb. 10, 2025
Abstract
Mitochondria
are
believed
to
have
originated
from
the
endosymbiosis
of
bacteria
and
they
still
contain
their
own
genome,
which
is
called
mitochondrial
DNA
(mtDNA).
Under
fluorescence
microscopy
cultured
mammalian
cells,
mtDNA
observed
as
numerous
tiny
dot-like
structures
nucleoids.
In
live-imaging,
morphology
distribution
nucleoids
changed
dynamically,
but
molecular
details
remain
poorly
understood.
this
study,
we
constructed
a
custom
siRNA
library
targeting
1,164
human
mitochondria-related
genes,
live-imaging-based
screening
HeLa
identified
that
calcium
uniporter
(MCU),
pore-forming
subunit
Ca2+
channel,
involved
in
nucleoid
morphology.
We
found
suppression
MCU
by
RNAi
induced
formation
highly
enlarged
well
respiratory
dysfunction
re-introduction
or
treatment
with
ionophore
recovered
These
results
suggest
uptake
via
associated
The
might
be
widely
applied
analyze
roles
proteins
various
cellular
events,
making
it
useful
understand
multifaceted
functions
mitochondria
cells.
Journal of Translational Medicine,
Journal Year:
2025,
Volume and Issue:
23(1)
Published: Feb. 20, 2025
Ovarian
aging
has
become
a
focal
point
in
current
research
on
female
and
refers
to
the
gradual
decline
ovarian
function
as
women
age.
Numerous
factors
influence
aging,
among
which
mitochondrial
is
one
because
it
plays
crucial
role
by
affecting
oocytes
granulosa
cells.
Mitochondrial
deterioration
not
only
leads
decrease
oocyte
quality
but
also
hinders
follicle
development,
further
impacting
women's
reproductive
health
fertility.
This
review
summarizes
integrates
impact
of
outlining
mechanisms
mitochondria
regulate
functions
study
aims
provide
potential
therapeutic
directions
mitigate
support
health.
According
2023
published
Cell,
such
oxidative
stress,
dysfunction,
chronic
inflammation,
telomere
shortening
collectively
drive
directly
Among
these
factors,
dysfunction
key
role.
reviewed
literature
from
databases
PubMed,
Google
Scholar,
CNKI,
using
keywords
"mitochondrial
dysfunction",
"decline
quantity",
"ovarian
aging",
aiming
summarize
theoretical
for
future
exploration
related
strategies.
The
main
characteristics
include
quantity
quality,
fluctuations
hormone
levels,
reduction
cell
function.
Studies
have
shown
that
affect
fertility
regulating
cellular
energy
metabolism,
exacerbating
causing
DNA
(mtDNA)
damage,
physiological
cells
within
ovary,
gradually
diminishing
reserve.
focuses
analyzing
effects
production
cells,
accumulation
reactive
oxygen
species
(ROS),
calcium
ion
(Ca2+)
concentration,
all
contribute
process,
understanding
them
will
new
insights
into
aging.
Therapeutic
interventions
targeting
may
help
delay
improve
Nature,
Journal Year:
2025,
Volume and Issue:
unknown
Published: April 9, 2025
Abstract
Mammalian
mitochondrial
DNA
(mtDNA)
is
replicated
by
polymerase
γ
(POLγ),
a
heterotrimeric
complex
consisting
of
catalytic
POLγA
subunit
and
two
accessory
POLγB
subunits
1
.
More
than
300
mutations
in
POLG
,
the
gene
encoding
subunit,
have
been
linked
to
severe,
progressive
conditions
with
high
rates
morbidity
mortality,
for
which
no
treatment
exists
2
Here
we
report
on
discovery
characterization
PZL-A,
first-in-class
small-molecule
activator
mtDNA
synthesis
that
capable
restoring
function
most
common
mutant
variants
POLγ.
PZL-A
binds
an
allosteric
site
at
interface
between
proximal
region
unaffected
nearly
all
disease-causing
mutations.
The
compound
restores
wild-type-like
activity
forms
POLγ
vitro
activates
cells
from
paediatric
patients
lethal
disease,
thereby
enhancing
biogenesis
oxidative
phosphorylation
machinery
cellular
respiration.
Our
work
demonstrates
small
molecule
can
restore
polymerases,
offering
promising
avenue
treating
disorders
other
severe
depletion
mtDNA.
