Mitochondrial Disorders and Transport Systems

Adenine Nucleotide Translocase

inner membrane, exports ATP into cytosol, ADP to matrix

Phosphate carrier

transmembrane protein, brings Pi into matrix to drive ATP synthesis

MELAS

most common, progressive and fatal

MELAS symptoms

lactic acidosis, myoclonus, ataxia, hearing loss, and epilepsy

MELAS cause

mutations in mitochondrial DNA encoding NADH Dehydrogenase, leading to deficiency

MELAS diagnosis

MRI for atrophy, increased lactate:pyruvate ratio, genetic testing

MERRF

rare, progressive myoclonus and seizures

MERRF symptoms

cerebellar ataxia, myopathy, arrythmia, hearing loss, dementia

MERRF diagnosis

ragged-red fibers in muscle tissue, clinical phenotypes, inheritance, CT, genetic testing

MERRF cause

point mutations in mtDNA, tRNA-Lys disrupting protein synthesis

LHON

rare, inherited form of vision loss from optic nerve deterioration

LHON cause

missence mutation in mtDNA affecting Complex I

LHON symptoms

central vision changes, loss of color vision, 90% male

LHON diagnosis

eye exam, genetic testing

NARP cause

specific point mutation, maternally inherited

NARP symptoms

NS affected, numbness/pain, progressive muscle weakness

Leigh syndrome

inherited metabolic disorder affecting CNS

Leigh Syndrome symptoms

appears in infancy, diarrhea, vomiting, dysphagia, failure to thrive, excess lactate

Leigh Syndrome cause

mutations in mtDNA or decreased PDC