Session 10: Organelles 3 - Mitochondria

Question 1

Explain the structure of the mitochondria.

Answer 1

Double membrane - important for maintaining ionic gradients
Intermembrane space - enzymes for phosphate transfer from ATP to other nucleotides
Outer membrane - lipid synthesis
Cristae - folding of the inner membrane
Matrix soluble materials between cristae

Question 2

What is the importance of the cristae?

Answer 2

• provides INCREASED surface area for biological function
• site for oxidative reactions of electron transport chain and ATP synthesis
• more folds –> more SA –> more ATP

Question 3

Describe the importance of matrix soluble materials between cristae.

Answer 3

These materials include the mitochondrial DNA genome and ribosomes.
- required because mitochondrial function is dependent on mito-DNA and nuclear DNA-encoded proteins (we need BOTH in order to function properly)

Question 4

How does mitochondria’s structure relate to its function?

Answer 4

Function: energy transfer - produces ATP
Double membrane - specialization for gradients bc of compartmentalization and increased surface area

Question 5

Explain the input of mitochondrial energy transfer.

Answer 5

Pyruvate and fatty acids are converted to acetyl CoA in the matrix

Question 6

Explain thru-put of energy transfer in the mitochondria.

Answer 6

Acetyl CoA is oxidized to CO2 via TCA cycle
- NAD –> NADH

Question 7

Explain output of energy via the ETC in the mito.

Answer 7

1) NADH electrons; NAD+ regenerated and returned to Krebs cycle
2) high energy electrons passed through the transport chain and pumps H+ out of matrix
3) H+ gradient across the membrane drives ATP synthase
*only possible with intact double membrane structure

Question 8

Relate mitochondrial function and calcium.

Answer 8

The mitochondria stores and regulates the release of intracellular calcium
- excessive release of Ca2+ can trigger apoptosis (programmed cell death)
- the level of calcium is usually HIGHER IN the mitochondria than the cytoplasm but doesn’t cause apoptosis
- Ca2+ is retained in the mito and is not released out –> no apoptosis

Question 9

Does the mitochondria have its own genome? What is its importance?

Answer 9

• ONLY mammalian organelles to have its own genome
• insufficient replication leads to cellular DYSFUNCTION
• circular genome in matrix –> encodes for things required for proper mito function

Question 10

Where does mitochondrial genome replication, transcription, and translation occur?

Answer 10

In the matrix of the mitochondria

Question 11

Does the mito genome encode all proteins necessary for mito function?

Answer 11

No. The mito must import nuclear-encoded proteins (genome info coming from the nucleus).

Question 12

What do drugs that target the mitochondria affect?

Answer 12

• respiratory function
• membrane pore and channel formation
• membrane function: Bcl-2 insertion
• mtDNA synthesis

Question 13

What does Ciprofloxacin affect?

Answer 13

Negatively affects mito-DNA synthesis
- treats anthrax (bacterial infection)

Question 14

What does Antimycin affect?

Answer 14

Inhibits the ETC by blocking flow of electrons (which is located the mito)
- used for chemotherapy

Question 15

Explain how Bcl-2 regulates mito membrane permeability.

Answer 15

Bcl-2 is a transmembrane protein present in the mitochondrial membrane
- helps maintain membrane integrity for respiration

Question 16

Explain how Bax regulates mito membrane permeability.

Answer 16

Bax is mostly located in the cytoplasm and some in the mito membrane.
- increases membrane permeability

Question 17

Describe how chemotherapy drugs affect Bax.

Answer 17

Cause translocation of Bax into the mito membrane
- Bax disrupts membrane potential (no electrochemical gradient) –> no ATP synthesis
- Bax also causes leakage of Ca2+ –> Ca2+ no longer retained in the mito –> activates calcium-dependent degenerative enzymes –> apoptosis

Question 18

What is HAART? What is its effect on HIV?

Answer 18

HAART - highly active anti-retroviral therapy (nucleoside analogues)
- inhibits HIV reverse transcriptase (converts viral RNA to DNA during HIV infection)
- negatively affects polymerase –> difficulty replicating mtRNA –> fewer mito genome copies –> ETC dysfunction
- also inhibits mito DNA polymerase (replicate mito DNA) –> clinical toxicity

Question 19

Why does HAART cause clinical toxicity?

Answer 19

HAART inhibits mito DNA polymerase (replication of DNA)
- mito DNA replication is not fast enough to replace usual mito turnover
- results in ETC deficiency –> no ATP (BAD)

Question 20

What is AZT (zidovudine)?

Answer 20

Nucleoside analog –> inhibits HIV reverse transcriptase