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18 Cards in this Set
- Front
- Back
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What metabolic processes take place in mitochondria?
List some other processes that take place in mitochondria |
Oxidative Phosphorylation
TCA cycle B-oxidation of Fatty Acids Proximal steps of Urea cycle Biosynth and degradation of some amino acids (BCAA) some steps of porphyrin biosynth Cholesterol metabolism estrogen testosterone homeostasis apoptosis ketogenesis |
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How many base pairs is the mitochondrial chromosome?
What is the structure of the mito chromosome? What does the mitochondrial DNA code for |
16 kb
37 genes: tRNA for translation polypeptides (for ETC) 12S and 16S rRNA |
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How can a mitochondrial disorder be inherited via Mendelian mechanisms?
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Although mitochondria chromosomes are maternally inherited, 300 nuclear DNA also codes for some mitochondrial proteins, including respiratory chain proteins.
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What are the most common clinical manifestations of Mitochondrial disease?
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Migraine, depression, and bowel dysmotility
Can be any organ system or any inheritance |
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Kearns-Sayre Syndrome (KSS)
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CPEO - chronic progressive external opthalmoplegia (weakness of eye muscles)
muscle weakness, onset before age 20, cardiac conduction defects, cerebellar ataxia |
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Name 4 Mitochondrial Diseases
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Kearns-Sayre Syndrome
Leigh Disease (subacute necrotizing encephalopathy) LHON (Leber's hereditary optic neuropathy) MELAS |
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Leigh Disease
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cranial nerve abnormalities, respiratory dysfunction, ataxia
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Leber's Heretidary Optic Neuropathy
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Presents as rapid central visual loss in adolescence or young adults. May also have dystonia.
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MELAS
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Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes. Onset 5-15 yrs old.
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What are key characteristics of a Mitochondrial Pedigree
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All children of affected females are affected
Some children may be unaffected or asymptomatic at a young age. No male transmission Male and female affected equally |
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What are 4 principles of maternal mitochondrial genetics
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Asexual - inherited from mothers only (high recurrence risk)
Heteroplasmy - varies from cell to cell, mutation and tissue dependent (different amount of normal and mutant mitochondria in different cells) Bottleneck - heteroplasmy is unstable, leads to different numbers of mutant in different offspring Threshold - some tissues need more energy than others |
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What steps are taken in making a mitochondrial diagnosis?
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Clinical phenotype
pedigree eval body fluid metabolic testing (for lactic acid, krebs intermediates) Absence of other causes Muscle biopsy (50% yield) Molecular diagnostics (mitochip) preventative treatment |
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What is a multifactorial trait?
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a phenotypic characteristic caused by both genetic and environmental factors
(complex trait) includes normal features such as height and intelligence, as well as abnormal - hypertension, autism, diabetes, isolated cleft lip and palate, schizophrenia, club foot, neural tube defects... |
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What are the characteristics of multifactorial disorders?
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familial concentration without set inheritance pattern
no clear biochemical defects from a particular gene variation in severity and expression, often with sex differences in frequency of occurence |
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What is the recurrence risk of multifactorial disorders?
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3-5% (due to germline mosaicism)
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Friedreich Ataxia
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FXN (FRDA, X25) - 96% homozygous GAA triplet repeat expansion in intron 1 of FXN gene
4% ar compound heterozygotes with GAA expansion and inactivating mutation in a different range of FXN |
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How many repeats are necessary for permutation and full mutation in Friedreich Ataxia?
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34-65 - premutation
66-1700 - full mutation |
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What causes the mitochondrial disease-like symptoms of Friedreich Ataxia?
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GAA repeat leads to low elves of frataxin (mitochondrial iron chaperone that shields iron from ROS and makes int bioavailable)
Frataxin is involved in iron sulfur clusters in the ETC complexes and Krebs cycle, and dysfunction leads to iron overload and mito dysfunction |
