Mitochondria DNA - mechanisms of toxicity

Question 1

What is the use of mitochondria?

Answer 1

OxPhos, biosynthesis of amino acids, nucleotides, steriod homrones and heme, oxidation of FAs and apoptotic cell death.

Question 2

Where and by what are mitochondrial proteins coded by?

Answer 2

nDNA and mtDNA and cystolically and mitochondrially

Question 3

Basic info about mtDNA

Answer 3

circular and small, 5-10 copies of mtDNA, ~1% of cellular DNA is mtDNA, no introns, point and missense mutations only, only maternal and not packed into chromatin and mutant phenotype = less ATP

Question 4

Why is mtDNA only maternal?

Answer 4

mitochondria of sperm cells are destroyed during fertilization

Question 5

What is homoplasmy and heteroplasmy of mtDNA?

Answer 5

homoplasmy refers to either WT or mutant mtDNA and heteroplasmy is a combination of two types of mtDNA.

Question 6

What is the threshold for mutations to present themselves?

Answer 6

Different for each cell dependent due to energy needs. sensitive to several factors including genetics, age and environment

Question 7

can nDNA mutations result in mitochondrial disorders?

Answer 7

Yes. nDNA is important in mitochondrial proteins

Question 8

What is LHONS?

Answer 8

disease resulting in death of optic nerves and loss of vision because of a mutation in NADH dehydrogenase

Question 9

What is MERRF?

Answer 9

Enzyme defects in the respiratory chain leading to epilepsy, deafness and dementia.

Question 10

What is kearns-sayre?

Answer 10

Large deletions in mtDNA resulting in several symptons including paralysis, retinal degeneration and seizures

Question 11

what is the clinical toxicity of retrovir?

Answer 11

it affects the skeletal muscle, bone marrow, liver, heart and can cause neuropathies

Question 12

how does doxorubicin cause cardiotoxicity?

Answer 12

Respiratory chain dysfunction causing generation (high) of ROS leading to interaction with mtDNA or other molecules resulting in cardiotoxicity