GROUP PRESENTATION ON

MITOCHONDRIAL-
ASSOCIATED DISEASES
PRESENTED BY- LUNIVA TULADHAR
SAJEENA KHATRI
PRAKRITI LAMICHHANE
 Our Team

LUNIVA TULADHAR PRAKRITI LAMICHHAN

SAJEENA KHATRI
Understanding the Powerhouses of
the Cell and Their Disorders
Mitochondria, nicknamed the "powerhouse
of the cell", are oval-shaped organelles
found in most eukaryotic cells. They are
essential for cell function because they
generate the majority of the cell's energy
currency, called adenosine triphosphate
(ATP), through a process called cellular
respiration.
 WHAT ARE MITOCHONDRIA?
STRUCTURE FUNCTION ROLES

Double Membrane: ATP Production: Apoptosis:

Mitochondria have two membranes: Mitochondria generates adenosine Mitochondria are involved in
an outer membrane and an inner triphosphate (ATP), the cell's main energy
programmed cell death, or
currency, through a process called
membrane. The inner membrane is apoptosis, by releasing factors that
oxidative phosphorylation.
folded into cristae, which increase the activate cell death pathways.
surface area for energy production.
Metabolic Regulation: Calcium Storage:
They play a critical role in various They help regulate intracellular
Matrix: metabolic pathways, including the citric calcium levels, which are important
The space enclosed by the inner acid cycle (Krebs cycle).
for various cellular processes,
membrane is called the matrix,
including muscle contraction .
containing enzymes, mitochondrial
DNA (mtDNA), and ribosomes.
 WHAT ARE
MITOCHONDRIAL
Mitochondrial diseases
are a group of
disorders caused by

DISEASES?
dysfunctional
mitochondria. These
diseases result from
mutations in
mitochondrial DNA
(mtDNA) or nuclear
DNA, which affect the
mitochondria's ability to
generate energy
efficiently.
 CAUSES
GENETIC MUTATIONS INHERITANCE

mtDNA Mutations: Maternal Inheritance:

Since mitochondria have their own DNA, mtDNA is inherited exclusively from the mother. Therefore,
mutations in mtDNA are passed down maternally.
mutations here can directly impair
mitochondrial function. Autosomal Recessive Inheritance:
Both parents carry and pass on a defective gene located in
Nuclear DNA Mutations: the nuclear DNA.

Mutations in nuclear genes can affect proteins

Autosomal Dominant Inheritance:
that are imported into mitochondria and are A single copy of a mutated gene from one parent is
crucial for their energy-producing activities. sufficient to cause the disease.
 TYPES
LEIGH MELAS MERRF KEARNS- CPEO
SYNDROME Mitochondrial Myoclonic Epilepsy with SAYRE Chronic Progressive

SYNDROME
A severe neurological Encephalomyopathy, Ragged-Red Fibers, External
disorder that typically Lactic Acidosis, and involving muscle twitches, Ophthalmoplegia, marked
Stroke-like episodes, seizures, and progressive A condition characterized by gradual paralysis of the
arises in infancy.
characterized by stroke- neurological issues. by progressive external eye muscles.
like episodes, muscle ophthalmoplegia
weakness, and (weakness of eye muscles),
neurological deficits. heart block, and other
systemic issues.
 LEIGH SYNDROME

CHARACTERISTICS SYMPTOMS DIAGNOSIS TREATMENT

Neurodegenerative: Developmental Delay Genetic Testing Supportive Care
It primarily affects the central
nervous system, including the Hypotonia Biochemical Tests Medications
brain and spinal cord.
Onset: Breathing problems MRI Scans Nutritional Support
Symptoms usually appear in the
first year of life but can sometimes Movement Disorders
present later. Blood and Urine
Respiratory
Progression: Tests
Seizures Support
The disease rapidly progresses,
with patients often experiencing
Feeding Difficulties
episodes of acute deterioration.
 MELAS
(MITOCHONDRIAL ENCEPHALOMYOPATHY,
LACTIC ACIDOSIS, AND STROKE-LIKE
EPISODES)
CAUSES SYMPTOMS DIAGNOSIS TREATMENT
Symptomatic
Mutations in Muscle weakness, Genetic Testing
pain, and fatigue Treatment
mitochondrial DNA are
Biochemical Tests
the culprit behind Recurrent Nutritional
MELAS. These mutations headaches Supplements
MRI and CT Scans
impair the function of
mitochondria, leading Vomiting and loss of L-Arginine
Muscle Biopsy
appetite
to cellular energy
Physical Therapy
deficiency, particularly Seizures
in the brain, muscles,
and other organs. Stroke-like episodes
Three patients with MELAS syndrome
 MERRF
(MYOCLONIC EPILEPSY WITH RAGGED-RED FIBERS)

CAUSES SYMPTOMS DIAGNOSIS TREATMENT

Mutations in Myoclonus Genetic Testing Symptomatic
Treatment
mitochondrial DNA are
Seizures Muscle Biopsy
responsible for MERRF. Nutritional
These mutations impair Ataxia Biochemical Tests Supplements
the function of
mitochondria, leading to Muscle weakness Electroencephalogram L-Arginine
(myopathy (EEG)
cellular energy deficiency,
Physical Therapy
particularly in the brain,
Hearing Tests
muscles, and other
organs.
 KEARNS-SAYRE SYNDROME

CAUSES SYMPTOMS DIAGNOSIS TREATMENT

Mutations in mitochondrial DNA Clinical Evaluation Cardiac
Progressive External
are the culprit behind KSS. Management
Ophthalmoplegia
These mutations disrupt the Genetic Testing
(PEO)
function of mitochondria, Endocrine
leading to cellular energy Muscle Biopsy Treatment
Pigmentary
deficiency in various organs.
Retinopathy
Unlike some other Cardiac Evaluation Nutritional
mitochondrial diseases, KSS Supplements
Cardiac Conduction
mutations are not typically Ophthalmologic
Defects
inherited and occur Examination
spontaneously during
development.
 CHRONIC PROGRESSIVE EXTERNAL
OPHTHALMOPLEGIA (CPEO)

CAUSES SYMPTOMS DIAGNOSIS TREATMENT

CPEO can occur due to several Surgical Intervention
Ptosis Clinical Evaluation
reasons:
Supportive Care
External Genetic Testing
Mitochondrial DNA
ophthalmoplegia Nutritional
mutations
Muscle Biopsy Supplements
Diplopia (double
Nuclear DNA mutations
vision) Blood Tests Ophthalmologic Care
Chronic progressive external
ophthalmoplegia
 TREATMENT
Unfortunately, there is no cure for mitochondrial diseases. However, there are
various treatment approaches that focus on managing symptoms and
improving quality of life for patients.
SYMPTOMATIC TREATMENT

MEDICATIONS
PHYSICAL THERAPY
OCCUPATIONAL THERAPY
SPEECH THERAPY
NUTRITIONAL SUPPORT
NUTRITIONAL SUPPLEMENTS

Coenzyme Q10
L-Carnitine
Riboflavin (Vitamin B2)
Thiamine (Vitamin B1)
Creatine
Arginine and Citrulline
EXPERIMENTAL AND EMERGING THERAPIES
Gene Therapy
Mitochondrial Replacement Therapy (MRT)
EPI-743 (Vincerinone)
Elamipretide (MTP-131)
 Conclusion
Mitochondrial diseases encompass a diverse group of disorders that arise from dysfunctions in the
mitochondria, the powerhouses of our cells. These diseases can profoundly impact multiple organ
systems, especially those with high energy demands like the brain, heart, and muscles. Common
mitochondrial disorders include Leigh Syndrome, MELAS, MERRF, Kearns-Sayre Syndrome, and Chronic
Progressive External Ophthalmoplegia (CPEO).

Mitochondrial diseases pose significant challenges due to their complexity and the broad range of
symptoms they cause. While current treatments focus primarily on symptom management and
improving patients' quality of life, ongoing research offers hope for more effective and targeted
therapies in the future. With continued effort and innovation, the future holds promise for better
outcomes and potentially curative therapies for mitochondrial diseases.
REFERENCES
https://www.umdf.org/
https://www.mitoaction.org/
https://rarediseases.org/
https://pubmed.ncbi.nlm.nih.gov/32310383/
Thank
you