Lecture 17 - Mitochondria in health and disease 2 Flashcards
name the 4 molecular mechanisms of ageing. in which mechanism does mitochondrial damage occurr?
DNA damage, RNA damage, Protein damage, membrane damage.
Mitochondrial damage occurs during DNA damage
at which 2 mitochondrial ETC complexes is the O2- radical generated ? what is it then converted to by superoxide dismutase 2?
1 and 3, to H2O2
H2O2 is detoxified to O2 by which molecule?
glutathione peroxidase 1
large scale mtDNA deletions are detected in ageing in post-mitotic cells located in …… (5 body parts)
muscle, heart, brain, skin, liver
point mtDNA mutations are detected in human mitotic cells located in ….. (7 body locations)
colon, stomach, small intestine, prostate, urothelium, liver, pancreas
in which body organ can both large scale mtDNA deletions and point mutations be detected?
liver
where are most mtDNA deletions found in the genome? what do the mutations remove (2 types of gene)?
in the major arc, remove protein encoding and tRNA genes
mtDNA point mutations subsitute how many base pairs? are they randomly located throughout the genome?
one, yes
name the 3 hypotheses related to clonal expansion of mutated mtDNA
survival of the smallest
survival of the slowest
random genetic drift
in the survival of the smallest mtDNA hypothesis, why do smaller mtDNA molecules as a result of a deletion out compete wild type molecules?
smaller = faster replication
in the survival of the slowest mtDNA hypothesis why do dysfunctional mitochondria survive?
have lower levels of oxidative damage so are not targeted by lysosomes
MtDNA deletions cause OXPHOS dysfunction in which group of neurons,
which is potentially linked to neuronal loss associated with ageing
substantia nigra
the dopaminergic neuron TFAM mutant has shown mtDNA depletion and slow progressive movement disorder similar to which neurodegenerative disease?
Psrkinson’s
