mitochondria 2 (hekimi) Flashcards
why does a dysfunctional mitochondria not produce uniform disease manifestations?
cause when theres a defect in mitochondria, the consequence will vary depending on the tissue
whats homoplasmy?
all the circular mitochondrial DNA in the mitochondria is normal (wild type), and unaffected (all the same)
whats heteroplasmy?
we have mutant and wild type circular DNA in the mitochondria
whats the difference between a stable heteroplasmy and a drift?
-stable heteroplasmy: replication rate of mutant DNA is equal to replication rate of wild type DNA
-drift: one replicates faster than the other, which can lead to mutant homoplasmy (mutation takes over and all the DNA in the mitochondria is mutant)
explain this
shows that c elegans that have a mutation in their ISP-1 gene live longer than c elegans who have the wild type
whats isp-1, and CTB-1
-they are both components of complex III of the ETC
-the mutation of the gene that codes for them affects lifespan and embryonic development time
what does the mutation isp-1(qm150) do?
it makes the c elegans live longer, but also slows down their embryonic dev
what does the mutation isp-1(qm150);ctb-1(qm189) do?
makes c elegans live longer, without slowing down their embryonic development, since the ctb mutation suppresses the longer development
true or false, we get our mitochodria through our father?
false, through mom
mitochondrial phenotypes related to mother
true or false, c elegans can only reproduce through self fertilization
false. a hemaphrodite (gives its oocyte) c elegan can also reproduce with a male c elegan (gives sperm) (c elegan that lost its x chromosome)
what will be the outcome? what does this experiment show?
shows that mitochondrial phenotype always passed from mother, via the oocyte (mitochondria cant pass through male germline)
true or false, when ctb mutation was discovered, it was thought to be heteroplasmic
false. they thought itwas homoplasmy cause the mutation was strongly favoured
what technique should be used if a mother with a sick mitochondria wants to have kids? explain it
-three parent baby technique
-mother’s nucleus of her oocyte cell is taken, and inserted into a healthy donor’s cell, who’s nucleus has been removed. we now have a healthy oocyte that contains healthy mitochondria and mother’s nucleus
-we can fuse this engineered oocyte with sperm cell, which will give rise to offspring
what does mitochondrial DNA code for?
-some proteins of the ETC
-mitochondrial tRNAS
-mitochondrial ribosomes
what are the 2 ways in which the degree of heteroplasmy can change?
-by selection due to an advantage for the cells to carry more copies of a mutant type
-by selection for or against a mutant copy due to the structure of the DNA (example: small copies might be favoured), Shorter mtDNA replicates faster, leading to an increase in mutant copies over generations.
what could be 2 reasons why two poeple with the same mitochondrial mutations have different phenotypes?
-difference in the degree of the heteroplasmy
-difference in their nuclear genomes, as the nuclear genome still codes for most of the mitochondrial proteins, which affects the way that the mitochondria interacts with the rest of the cell
what are these 2 processes called (top and bottom)
top: fusion
bottom: fissure
what do we mean by, fission and fusion mutants have opposite phenotypes?
mitochondria takes diff shape depending on if fusion or fission affected
which mutation in mitochondria leads to having no fusion?
mfn-null
which mutation in mitochondria leads to having no fission?
-DRP1-K38A
what do we mean by the degree of fragmentation of the mitochondria is linked to functional state?
-degree to which mitochondria are fused has to do with the state of the cell
-if cell is stressed (low ATP production), more fragmented/separated
-if highly ATP producing, mitochondria would tend to be very connected and filamentous
true or false, in normal functioning cells, superoxide is controlled, and isnt a problem
true
how do reactive oxygen species (such as superoxide) occur in the cell? are they useful in any way?
-they are a by-product of metabolism
-they are useful as they can act a signalling molecules
-some enzymes make superoxide/ hydrogen peroxide on purpose, which proves that they are useful
which enzymes make superoxide/ hydrogen peroxide on purpose?
NADPH oxidases (NOX)
how can we rescue/ remove a damaged mitochondria
remove: mitophagy
save: fusion and then fission
why is fission important?
promotes equal segregation of mitochondria into daughter cells
-for cell division, want to make sure we have enough mitochondria so that when we separate, both daughter cells get mitochondrion
true or false, the mitochondria never comes into contact with ER
false
why is it important for the mitochondria to make contact with the endoplasmic reticulum?
-come into close opposed contact, called mitochondrial associated membrane
-these regions participate in calcium homostasis, its a place where calcium gets exchanged, since both mitochondria and ER contain calcium
-these regions are also important for the export of certain molecules that are difficult to transport cause so hydrophobic (ex: lipids)
-these substances exported through ER after mitochondria makes them
true or false, mitochondria makes lipids
true
where does fission often occur in the mitochondria?
at the point of ER mitochondrial contact
how do cells degrade their mitochondria? explain the process?
-mitophagy, which is a type of autophagy
-the mitochondria is brought to a lysosome, in order to be destroyed
why is mitophagy important?
-clears out dysfunctional mitochondria, to prevent it from hurting the other mitochondria in the cell
-if we have too much superoxide in the mitochondria it can destroy it
