Lecture 20 - Mitochondrial Diseases Flashcards
<p>The outer membrane of mitochondria is permeable to:</p>
<p>many small molecules</p>
<p>The inner membrane of mitochondria is impermeable to:</p>
<p>small molecules, even protons (H+)</p>
<p>Cells in different tissues have vastly differing mitochondrial content depending on:</p>
<p>energy requirements</p>
<p>The primary (general) function of the mitochondria is:</p>
<p>the oxidation of fuel molecules to produce ATP</p>
<p>The secondary (general) functions of the mitochondria are: (list 8)</p>
<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>
What secondary function of mitochondria relies on cytochrome P450 enzymes that are present in the mitochondria?
Steroid and bile synthesis
Also acceptable: hydroxylation of steroid molecules and bile acids
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?
Ketogenesis
What two secondary functions of mitochondria are localized to hepatic mitochondria?
- Ketogenesis
2. Urea Cycle
What is the function of the dihydroorotate dehydrogenase enzyme?
de novo biosynthesis of pyrimidines
What is the location of the dihydroorotate dehydrogenase enzyme?
inner mitochondrial membrane
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.
heme synthesis
In what part of the mitochondria does heme synthesis take place?
mitochondrial matrix
Cytoplasmic calcium homeostatis plays an important role in:
synaptic transmission
_________ is a tightly regulated cellular pathway that is activated by a group of cysteine proteases known as caspases.
Apoptosis - programmed cell death
What is homoplasmy?
All the mitochondrial genomes have the same DNA sequence
What is heteroplasmy?
heterogeneity of mitochondrial genomes
Which exhibit a higher mutation rate - mitochondrial genes or nuclear genes?
Mitochondrial genes
3 proposed reasons for high mutation rates in mitochondrial genes:
- lower fidelity DNA replication machinery
- less efficient DNA repair systems
- higher exposure to reactive oxygen species
What are the two hallmarks of maternal inheritance?
- all children of an affected mother are affected
2. none of the children of an affected male are affected
________ _________ is the term used to describe when each daughter cell receives different proportions of normal and mutant genomes in cells exhibiting heteroplasmy.
replicative segregation
Cells bearing a pathogenic mt DNA mutation can usually tolerate _______ without experiencing deleterious consequences.
a relatively high percentage of the mutant DNA
A significant percentage of people with mutations in the genes responsible for LHON are asymptomatic, which suggests:
a high threshold effect
Mitochondrial diseases have the greatest impact on what type of tissues?
Tissues with high energy demands: nervous system, muscle, heart, kidney, and liver
The symptoms of _______ include muscle weakness and pain, recurrent headaches, loss of appetite, vomiting, and seizures linked to a build-up in lactic acid.
MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes)
While the consequences of a deficiency in mitochondrial function are diverse, the most common defect observed is:
decreased energy production
________ is a mitochondrial disease that includes symptoms of myoclonus, myopathy, and progressive stiffness.
MERRF (myoclonic epilepsy with ragged-red fibers)
Most patients with MERRF have mutations in what gene?
mitochondrial lysine tRNA gene (MT-TK)
_______ is a mitochondrial disease that generally presents in childhood or early adulthood with sensory neuropathy, myopathy, and ataxia.
NARP (neuropathy ataxia, and retinitis pigmentosa)
_____ 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.
Leigh disease
A mitochondrial disorder with variable penetrance can best be explained by:
heteroplasmy and replicative segregation
