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Flashcards in Lecture 23 Deck (18):

Where are the majority of Mitochondrial resident proteins found?

In the mitochondria matrix


What are the key differences between nuclear genome encoded proteins destined for the ER vs proteins destined for the Mitochondria?

Those destined for the mito are post-translationally translocated into the mito, whereas ER destined proteins are co-translationally translocated. Also, N-terminal signal sequence is specific to each organelle for their specific proteins (positively charged for mito destined and hydrophobic for ER.) Keep in mind that proteins that translocate into the mito undergo folding in the mito to reach their proper form.


What are the characteristics of the mitoDNA that code for approx 13 mito proteins (those used in the ETC)?

The mitoDNA is circular, located near the innermembrane, and there are multiple copies of the mitoDNA within each mito


What are the inhibitors of nuclear DNA (nDNA) and mito DNA (mtDNA) that encode mito proteins?

Cyclohexamide inhibits cytosolic translation elongation of nDNA encoded proteins, while Chloramphenicol inhibits mitochondrial petidyl transferase activity during translation of mtDNA encoded mRNA .


Which strand of the mtDNA are most of the genes encoded on?

Heavy Strand


What are the 3 things the mtDNA code for?

1. 13 proteins used in the ETC
2. rRNA
3. tRNA


Which complex in the ETC is the only one encoded solely by nDNA?

Complex II


What are the 4 pillars of mito genetics, and what do they refer to?

1. Maternal inheritance only
2. Heteroplasmy --> Different mitochondria may have different genomes within the same individual or even within the same tissue.
3. Stochastic (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.)
4. Threshold effect --> different tissues have different energetic needs and will respond differently to whichever assortment of mito their cells have.


How is paternal mtDNA kept from being passed on?

Selective degradation in the ovum of paternal mtDNA


At which complexes can ROS (reactive O2 species) be formed in the ETC

At complex I (within the matrix) and at complex III (in matrix and intermembrane space.)


How does the mito control ROS produced by the ETC?

Superoxide radicals can be converted to H2O2 by MnSOD (manganase superoxide dismutase) --> H2O2 can be further converted to H2O and O by catalase.


What can be produced from H2O2 and Fe2+ in the mito, and what are its effects?

H2O2 in the mito can combine with Fe2+ (mito produces heme) and form an OH radical. The OH radical can damage proteins, 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 is necessary for immune response, but chronic oxidative stress when old leads to dysfunction.


What are the 4 diseases we covered associated mtDNA mutation?

3. Leigh Syndrome


What's the difference between affected areas of the body between MELAS and LHON and what does this imply?

MELAS affects many parts/systems, while LHON is specific to the eye. This implies that mitochondrial issues could affect many different parts/systems or they could be tissue specific.


How do the causes of Leigh Syndrome and Alpers disease contrast, and what does this indicate?

Leigh Syndrome can be caused by issues with mtDNA OR by issues with nDNA. Alpers disease (progressive loss of mtDNA in an individual due to loss of mtDNA POLG) is caused solely because of an issue with nDNA. So, issues with either or both mtDNA/nDNA can cause mitochondrial issues.


What is MERRF characterized by and what is the causative mutation?

It is characterized by "ragged red fibers" of muscle tissue, and it is caused by an A to G point mutation.


What are the steps in mtDNA replication?

1. POLRMT --> synthesizes primer on light strand promoter.
2. Displaced heavy strand coated with mtSSB.
3. Twinkle --> mtDNA helicase unwinds
4. POLG (pol gamma - alpha catalytic subunit; beta subunit for promoter recognition) --> synthesizes nascent strand with high fidelity because has 3'-->5' exonuclease activity.