Lecture 23 Flashcards
The majority of Mitochondrial resident proteins are found in the ____.
Matrix
Mitochondial proteins created from nuclear DNA is ____-translationally translocated into the mito. The ___-termial sequences for an _____ helix (one positively charged face and one non-polar face.) The polar face binds to the translocation machinery. In contrast, ER destined proteins made from nuclear DNA have _____ N-terminal sequences. Keep in mind mito proteins undergo folding in the _____.
Post-translationally
N-terminal
Amphipathic
Hydrophobic (nonpolar)
Folding
mtDNA is _____ in shape located near the ______, and there are multiple copies of mtDNA within each mito.
Circular
Innermembrane
_______ inhibits cytosolic translational elongation of nuclear DNA. ______ inhibits mitochondrial peptidyl transferase activity.
Cyclohexamide
Chloramphenicol
Which strand of the mtDNA are most of the genes encoded on and what is the structure this strand forms that regulates mtDNA transcription?
Heavy Strand
D-loop
What are the 3 things the mtDNA code for? Note: mtDNA has no _____ sequences (codes for polycistronic mRNA).
- 13 proteins used in the ETC
- rRNA
- tRNA
Intron
Which complex in the ETC is the only one encoded solely by nDNA?
Complex II
4 pillars of mtDNA genetics:
- ______ inheritance only
- ______ –> Different mitochondria may have different genomes within the same individual or even within the same tissue.
- ______ (random) segregation –> gametes can inherit different mitochondrial composition (i.e. if mom has 5 mutant mitos out of 20, she could pass all 5 mutants to one gamete, she could pass 2 mutants to one and 3 to another, so on and so forth.)
- _______ effect –> different tissues have different energetic needs and will respond differently to whichever assortment of mito their cells have.
- Maternal
- Heteroplasmy
- Stochastic
- Threshold effect
How is paternal mtDNA kept from being passed on?
Selective degradation in the ovum via ubiquitination and degradation via the 26S proteosome.
At which complexes can ROS (reactive O2 species) be formed in the ETC, and how might it enter the cytosol?
At complex I (within the matrix) and at complex III (in matrix and intermembrane space.) If created on the intermembranse space side of Complex III, it can diffuse into the cytosol.
_____ _____ _____ converts superoxide radicals into H2O2. _____ converts H2O2 to H2O and O2
Manganese superoxide dismutase
Catalase
What can be produced from H2O2 and Fe2+ in the mito, and what are its effects? Remember that it is the most damaging ROS.
H2O2 in the mito can combine with Fe2+ (mito produces heme) and form an OH radical. The OH radical can damage proteins (oxidize disulfide bonds, more so in the ER than cytosol), lipids and DNA (both mtDNA and nDNA particularly by forming 8-oxoguanine.)
Why might ROS be good when young but not when old?
Transient oxidative stress can facilitate the innate immune response, but chronic oxidative stress when old leads to dysfunction (like inflammation/arthritis).
MERRF disease is characterized by _____. MELAS is characterized by ______, lactic acidosis, and stroke-like episodes. LHON is characterized by _____ neuropathy. Leigh Syndrome is characterized by severe neurological and ______ failure. These 4 mito diseases are caused by _____ mutations.
Pearson syndrom is characterized by anemia and pancreatic and _____ dysfunction. Kearns Sayre Syndrome is characterized by paralysis of the ____ muscles, and retinopathy.
All but Pearson and LHON are associated with RRF (___ ___ ___). These two are associated with large scale and “common” _______, respectively.
Epilepsy
Encephalomyopathy
Optic neuropathy
Respiratory
Point mutations
Liver
Eye
Ragged Red Fibers
Deletions
What are the steps in mtDNA replication?
- Topoisomerase eases torsion and opens D-loop in heavy chain.
- POLRMT –> synthesizes primer on light strand promoter.
- . Twinkle –> mtDNA helicase unwinds
- Displaced heavy strand coated with mtSSB.
- POLG (pol gamma - alpha catalytic subunit; beta subunit for promoter recognition) –> synthesizes nascent strand with high fidelity because has 3’–>5’ exonuclease activity.
