Abstract
Mitochondria
are
the
foundation
of
cellular
energy
metabolism
and
crucial
for
cell
growth
development.
Mitochondrial
dysfunction
can
disrupt
normal
functions,
contributing
to
onset
related
diseases.
The
functionality
mitochondria
is
influenced
by
various
associated
proteins
molecules,
including
mitofusin
2,
optic
atrophy
1,
dynamin
protein
translocase
inner
membrane
23,
outer
40,
PTEN‐induced
kinase
reactive
oxygen
species
modulator
nicotinamide
adenine
dinucleotide
dehydrogenase,
mitochondrial
voltage‐dependent
anion
channel
DNA.
We
also
discussed
role
targeting
sequences
in
proteins.
abnormal
expression
these
molecules
impair
network
remodeling,
which
essential
maintaining
quantity
quality
facilitating
exchange
substances
between
them.
This
review
elucidates
relationship
dysfunction‐induced
diseases,
outlines
current
methods
detecting
networks
thereby
providing
strategies
study
‐related
Medicina,
Год журнала:
2023,
Номер
59(3), С. 608 - 608
Опубликована: Март 19, 2023
Background.
Defects
of
mitochondrial
DNA
(mtDNA)
involved
in
the
function
electron
transport
chain
can
result
primary
diseases
(PMDs).
Various
features
influence
phenotypes
different
PMDs,
with
relevant
consequences
on
clinical
presentation,
including
presence
hearing
impairment.
This
paper
aims
to
describe
loss
related
and
when
possible,
their
phenotype.
Methods.
A
systematic
review
was
performed
according
PRISMA
guidelines,
searching
Medline
until
December
2022.
total
485
papers
were
identified,
based
specified
criteria,
7
included
this
study.
Results.
759
patients
affected
by
PMDs
included.
The
age
ranged
from
2
days
78
years
old,
male-to-female
ratio
1.3:1.
percentage
subjects
40.8%,
(310/759),
most
cases,
impairment
described
as
sensorineural,
bilateral,
symmetrical,
progressive,
presentations
depending
syndrome
severity.
Conclusions.
are
challenging
conditions
phenotypes.
Hearing
loss,
especially
bilateral
may
represent
a
red
flag;
its
association
other
systemic
disorders
(particularly
neuromuscular,
ocular,
endocrine)
should
alert
clinicians,
confirmation
via
genetic
testing
is
mandatory
nowadays.
New England Journal of Medicine,
Год журнала:
2024,
Номер
390(15), С. 1421 - 1430
Опубликована: Апрель 17, 2024
A
58-year-old
woman
was
transferred
to
the
hospital
after
16
months
of
waxing
and
waning
confusion
aphasia
evolving
changes
on
MRI
head.
diagnosis
made.
Biomolecules,
Год журнала:
2024,
Номер
14(12), С. 1524 - 1524
Опубликована: Ноя. 28, 2024
Mitochondrial
encephalopathy,
lactic
acidosis,
and
stroke-like
episodes
(MELAS)
syndrome
is
a
complex
mitochondrial
disorder
characterized
by
wide
range
of
systemic
manifestations.
Key
clinical
features
include
recurrent
episodes,
seizures,
muscle
weakness,
exercise
intolerance,
sensorineural
hearing
loss,
diabetes,
progressive
neurological
decline.
MELAS
most
commonly
associated
with
mutations
in
DNA,
particularly
the
m.3243A>G
mutation
MT-TL1
gene,
which
encodes
tRNALeu
(CUR).
These
impair
protein
synthesis,
leading
to
defective
oxidative
phosphorylation
energy
failure
at
cellular
level.
The
presentation
severity
vary
widely
among
patients,
but
often
results
significant
morbidity
reduced
life
expectancy
because
deterioration.
Current
management
largely
focused
on
conservative
care,
including
anti-seizure
medications,
arginine
or
citrulline
supplementation,
high-dose
taurine,
dietary
therapies.
However,
these
therapies
do
not
address
underlying
genetic
mutations,
leaving
many
patients
substantial
disease
burden.
Emerging
experimental
treatments,
such
as
gene
therapy
replacement
techniques,
aim
correct
defects
offer
potential
curative
strategies.
Further
research
essential
understand
pathophysiology
MELAS,
optimize
current
therapies,
develop
novel
treatments
that
may
significantly
improve
patient
outcomes
extend
survival.
International Journal of Molecular Sciences,
Год журнала:
2022,
Номер
24(1), С. 124 - 124
Опубликована: Дек. 21, 2022
Mitochondrial
myopathies
represent
a
heterogeneous
group
of
diseases
caused
mainly
by
genetic
mutations
to
proteins
that
are
related
mitochondrial
oxidative
metabolism.
Meanwhile,
similar
etiopathogenetic
mechanism
(i.e.,
deranged
phosphorylation
and
dramatic
reduction
ATP
synthesis)
reveals
the
evolution
these
show
significant
differences.
However,
some
physiological
pathophysiological
aspects
mitochondria
often
reveal
other
potential
molecular
mechanisms
could
have
pathogenetic
role
in
clinical
disorders,
such
as:
i.
ROS
production
both
term
signaling
terms
damaging
molecules;
ii.
severe
modifications
nicotinamide
adenine
dinucleotide
(NAD)+/NADH,
pyruvate/lactate,
α-ketoglutarate
(α-KG)/2-
hydroxyglutarate
(2-HG)
ratios.
A
better
definition
at
basis
their
pathogenesis
improve
not
only
approach
diagnosis,
prognosis,
therapy
but
also
deepen
knowledge
medicine
general.
Human Molecular Genetics,
Год журнала:
2023,
Номер
33(5), С. 465 - 474
Опубликована: Ноя. 21, 2023
Abstract
Whole
genome
sequencing
(WGS)
from
large
clinically
unselected
cohorts
provides
a
unique
opportunity
to
assess
the
penetrance
and
expressivity
of
rare
and/or
known
pathogenic
mitochondrial
variants
in
population.
Using
WGS
179
862
individuals
UK
Biobank,
we
performed
extensive
single
variant
aggregation
association
analyses
15
881
mtDNA
73
with
disease-relevant
phenotypes.
We
identified
12
homoplasmic
one
heteroplasmic
(m.3243A>G)
genome-wide
significant
associations
our
cohort.
Heteroplasmic
m.3243A>G
(MAF
=
0.0002,
variant)
was
associated
diabetes,
deafness
heart
failure
increased
aspartate
aminotransferase
levels
including
three
low-frequency
~0.002
beta~0.3
SD).
Most
disease
(n
66/74)
were
population
(<1:9000).
Aggregated
or
analysis
showed
low
settings
for
relevant
phenotypes,
except
m.3243A>G.
Multi-system
risk
greatly
level
≥
10%.
The
odds
ratio
these
traits
5.61,
12.3
10.1
25.1,
55.0
39.5,
respectively.
Diabetes
further
influenced
by
type
2
diabetes
genetic
risk.
Our
study
variation
large-unselected
novel
demonstrated
that
have
lower
settings.
an
exception
at
higher
heteroplasmy
showing
impact
on
health
making
it
good
candidate
incidental
reporting.
Current Opinion in Endocrinology Diabetes and Obesity,
Год журнала:
2023,
Номер
unknown
Опубликована: Дек. 4, 2023
Primary
mitochondrial
diseases
are
one
of
the
most
prevalent
groups
multisystem
genetic
disorders.
Endocrinopathies
associated
with
may
have
clinical
features
that
distinct
from
more
common
forms.
We
provide
an
overview
disorder
genetics
and
phenotypes,
focusing
on
recent
studies
regarding
identification
treatment
endocrinopathies.
Frontiers in Cardiovascular Medicine,
Год журнала:
2023,
Номер
10
Опубликована: Апрель 17, 2023
Mitochondrial
disease,
most
cases
of
which
are
caused
by
mitochondrial
DNA
(mtDNA)
mutation,
is
present
with
multiple
phenotypes
including
diabetes
mellitus,
sensorineural
hearing
loss,
cardiomyopathy,
muscle
weakness,
renal
dysfunction,
and
encephalopathy,
depending
on
the
degree
heteroplasmy.
While
mitochondria
play
an
important
role
in
intracellular
glucose
lactate
metabolism
insulin-sensitive
tissues
such
as
muscles,
appropriate
strategies
for
glycemic
control
have
not
yet
been
established
a
patient
often
complicated
myopathy.
Here,
we
describe
history
40-year-old
man
mtDNA
3243A
>
G
who
had
wasting,
mellitus
stage
3
chronic
kidney
disease.
He
developed
mild
diabetic
ketoacidosis
(DKA)
process
treatment
poor
severe
latent
hypoglycemia.
According
to
standard
therapy
DKA,
he
was
treated
continuous
intravenous
insulin
infusion
therapy,
unexpectedly
resulted
abrupt
transient
elevation
blood
levels
without
exacerbation
heart
failure
function.
Since
determined
balance
between
production
consumption,
following
injection
may
reflect
only
enhanced
glycolysis
dysfunction
but
also
decreased
consumption
sarcopenic
skeletal
failing
heart.
Intravenous
patients
disease
unmask
derangements
response
signaling.
