mitochondria Flashcards
what is a mitochondria
Sub-cellular organelles responsible for producing the majority of cellular ATP via the oxidative phosphorylation pathway
MtDNA is a 16.6kb circular dsDNA molecule encoding for 37 genes: 13 polypeptides of the OXPHOS system, 2 ribosomal RNAs and 22 tRNAs
MtDNA is almost exclusively transmitted through the maternal line.
discuss the mutation rate in mitochondria
Higher mutation frequency (~10x) than nDNA
The mtDNA can all be identical (homoplasmy) or a mixture of two or more mt genotypes (heteroplasmy).
The percentage level of mutant mtDNA may vary among individuals within the same family, and also among organs and tissues within the same individual
Discuss mutation thresholds in mt
In cases of heteroplamic muts there is typically a threshold level where the mutation becomes clinically significant
50-60% for deleted mtDNA molecules;
>90% point mutations in tRNA.
describe clinical features of MELAS (Mitochondrial encephalopathy, lactic acidosis and stroke-like episodes)
Myopathy, encephalopathy, lactic acidosis, stroke-like episodes
MT-TL1 m.3243A>G and m.3271T>C
describe clinical features of MERFF (Myoclonic epilepsy and ragged-red fibres)
Myoclonic epilepsy, myopathy, cereberal ataxia
MT-TK m.8344A>G and m.8356T>C
describe clinical features of NARP (Neurogenic weakness, ataxia and retinitis pigmentosa)
Sensory neuropathy, ataxia, retinitis pigmentosa
MT-ATP6 m.8993T>G
describe clinical features of Leigh/Leigh like
Encephalopathy, lactic acidosis
MT-ATP6 m.8993T>C
How are mt disorders diagnosed
multidiscipline approach involving clinical assessment, family history, biochemical testing, histopathological examination and direct molecular testing.
Histochemistry specific mt enzymes.
Biochemistry measure rates of flux, substrate oxidation and ATP production
Molecular genetics long-range PCR is typical front line test ( point mut, dels, dups and multiple mtDNA dels)
