Lecture 20 - Mitochondrial Diseases

Question 1

<p>The outer membrane of mitochondria is permeable to:</p>

Answer 1

<p>many small molecules</p>

Question 2

<p>The inner membrane of mitochondria is impermeable to:</p>

Answer 2

<p>small molecules, even protons (H+)</p>

Question 3

<p>Cells in different tissues have vastly differing mitochondrial content depending on:</p>

Answer 3

<p>energy requirements</p>

Question 4

<p>The primary (general) function of the mitochondria is:</p>

Answer 4

<p>the oxidation of fuel molecules to produce ATP</p>

Question 5

<p>The secondary (general) functions of the mitochondria are: (list 8)</p>

Answer 5

<p>1. Ketogenesis

2. Urea cycle
3. Amino acid catabolism
4. Pyrimidine biosynthesis
5. Steroid and bile synthesis
6. Heme synthesis
7. Calcium homeostasis
8. Apoptotic signaling</p>

Question 6

What secondary function of mitochondria relies on cytochrome P450 enzymes that are present in the mitochondria?

Answer 6

Steroid and bile synthesis

Also acceptable: hydroxylation of steroid molecules and bile acids

Question 7

What secondary function of mitochondria is a process in which fatty acids are converted to smaller, water soluble fuel molecules that are important during periods of starvation?

Answer 7

Ketogenesis

Question 8

What two secondary functions of mitochondria are localized to hepatic mitochondria?

Answer 8

1. Ketogenesis

2. Urea Cycle

Question 9

What is the function of the dihydroorotate dehydrogenase enzyme?

Answer 9

de novo biosynthesis of pyrimidines

Question 10

What is the location of the dihydroorotate dehydrogenase enzyme?

Answer 10

inner mitochondrial membrane

Question 11

The first step of __________, which takes place in the liver and bone marrow, is condensation of the amino acid glycine with succinyl-CoA, an intermediate in the TCA cycle.

Answer 11

heme synthesis

Question 12

In what part of the mitochondria does heme synthesis take place?

Answer 12

mitochondrial matrix

Question 13

Cytoplasmic calcium homeostatis plays an important role in:

Answer 13

synaptic transmission

Question 14

_________ is a tightly regulated cellular pathway that is activated by a group of cysteine proteases known as caspases.

Answer 14

Apoptosis - programmed cell death

Question 15

What is homoplasmy?

Answer 15

All the mitochondrial genomes have the same DNA sequence

Question 16

What is heteroplasmy?

Answer 16

heterogeneity of mitochondrial genomes

Question 17

Which exhibit a higher mutation rate - mitochondrial genes or nuclear genes?

Answer 17

Mitochondrial genes

Question 18

3 proposed reasons for high mutation rates in mitochondrial genes:

Answer 18

1. lower fidelity DNA replication machinery
2. less efficient DNA repair systems
3. higher exposure to reactive oxygen species

Question 19

What are the two hallmarks of maternal inheritance?

Answer 19

1. all children of an affected mother are affected

2. none of the children of an affected male are affected

Question 20

________ _________ is the term used to describe when each daughter cell receives different proportions of normal and mutant genomes in cells exhibiting heteroplasmy.

Answer 20

replicative segregation

Question 21

Cells bearing a pathogenic mt DNA mutation can usually tolerate _______ without experiencing deleterious consequences.

Answer 21

a relatively high percentage of the mutant DNA

Question 22

A significant percentage of people with mutations in the genes responsible for LHON are asymptomatic, which suggests:

Answer 22

a high threshold effect

Question 23

Mitochondrial diseases have the greatest impact on what type of tissues?

Answer 23

Tissues with high energy demands: nervous system, muscle, heart, kidney, and liver

Question 24

The symptoms of _______ include muscle weakness and pain, recurrent headaches, loss of appetite, vomiting, and seizures linked to a build-up in lactic acid.

Answer 24

MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes)

Question 25

While the consequences of a deficiency in mitochondrial function are diverse, the most common defect observed is:

Answer 25

decreased energy production

Question 26

________ is a mitochondrial disease that includes symptoms of myoclonus, myopathy, and progressive stiffness.

Answer 26

MERRF (myoclonic epilepsy with ragged-red fibers)

Question 27

Most patients with MERRF have mutations in what gene?

Answer 27

mitochondrial lysine tRNA gene (MT-TK)

Question 28

_______ is a mitochondrial disease that generally presents in childhood or early adulthood with sensory neuropathy, myopathy, and ataxia.

Answer 28

NARP (neuropathy ataxia, and retinitis pigmentosa)

Question 29

_____ is a severe neurological disorder that presents in the first year of life; vomiting, diarrhea, dysphagia, and failure to thrive, along with lesions in the basal ganglia, are a common symptom presentation.

Answer 29

Leigh disease

Question 30

A mitochondrial disorder with variable penetrance can best be explained by:

Answer 30

heteroplasmy and replicative segregation