Gen Mitochondrial Mastick Flashcards
What are the tissues most dependent on oxidative phosphorylation (i.e need mitochondrias)?
heart, skeletal muscles, and CNS
Mitochondrial disorders often manifest as what?
myopathies (muscle),neuropathies (neurons), and encephylopathies (brain)
Mitochondrial dysfunction is also linked to what disorder?
diabetes mellitus
What is mitochondrial function influenced by?
1) Capacity for oxidative phosphorylation (nuclear and mito genes)
2) Tissue specific req.
3) age (cap. for OP decreases with age, i.e accumulation of mtDNA mutations)
4) Accumulation of somatic mtDNA mutations and degree of heteroplasmy
What do you call this:
The situation in which, within a single cell, there is a mixture of mitochondria (energy producing cytoplasmic organelles), some containing mutant DNA and some containing normal DNA
heteroplasmy
mitochondrial disorders are often (blank) or do not manifest until adulthood.
progressive
Mitochondrial function is sufficent at (blank) but deteriorates with age (normal) and accumulation of additional mutant alleles.
birth
How big is mtDNA and what does it encode?
How many nuclear DNA proteins are imported into the cell to participate in oxidative phosphorylation?
16.5 kb, encodes rRNAs, tRNAs, and 13 proteins
90
in mitochondrial disorders to males or females pass on their mutations?
females only
What are these major attributes of:
Usual recurrence risk:
affected mothers: 100% children inherit mutation.
affected fathers: 0% of children inherit mutation.
Transmission pattern: vertical; disease phenotype seen in generation after generation.
Sex ratio: equal numbers of affected males and females.
Other: progressive diseases, delayed age of onset,
highly variable expression (due to heteroplasmy).
Major attributes of mitochondrial inheritance patterns
(blank) inheritance is hallmark of mitochondrial inheritance.
maternal
all mitochondria come from the (blank)
egg
Name that disease:
Mitochondrial disorder with rapid loss of central vision due to death of the optic nerve. Delayed age of onset, 20-30 years old. 95% of cases caused by one of three missense mutations in a mitochondrial protein (mtDNA protein complex I).Heteroplasmy is rare. Expression is relatively uniform.
Leber’s hereditary optic neuropathy (LHON)
What is caused by one of three missense mutations in a mitochondrial protein (mtDNA protein complex I)
Leber’s hereditary optic neuropathay (LHON)
Name that Disease:
Four “canonical” features: Myoclonus, generalized epilepsy, ataxia, ragged-red fibers (RRF) in the muscle biopsy.
Frequent manifestations: Sensorineural hearing loss, peripheral neuropathy, dementia, short stature, exercise intolerance, optic atrophy
Mutation: single base changes in mitochondrial tRNA molecules that change their codon specificity.
MERRF (myoclonic epilepsy with ragged-red fiber)