Mitochondrial Pharmacology

Question 1

What are the 4 main compartments of mitochondria?

Answer 1

1. Outer membrane (permeable to certain ions and small molecules)
2. Inner membrane space
3. Inner membrane (folded into cristae, mechinery for OXPHOS)
4. Matrix-location for metabolic reactions

Question 2

Mutations in mtDNA only affect..

Answer 2

the integrity of the respiratory chain

Question 3

Mutations in nuclear DNA……

Answer 3

disturb OXPHOS, by impairing mitochondrial protein import, translation and assembly

Question 4

Fusion is regulated by what proteins

Answer 4

Mitofusins (MFN1 and MFN2) and optic atrophy protein 1 (OPA1)

Question 5

Fission is controlled by what proteins

Answer 5

Including dynamin-related protein (DRP1)

Question 6

Which drug is an OXPHOS modulator that is a synthetic short chain analogue of coenzyme Q10 with enhanced solubility and pharmacokinetics.

Answer 6

Idebenone (Raxone)

Question 7

Which drug (OXPHOS modulator had disappointing results in trials for AD but promising results for the treatment of Leber’s hereditary optic neuropathy (LHON)

Answer 7

Idebenone (Raxone)

Question 8

Which OXPHOS modulator is a competitive inhibitor of complex 1 and restores the hyperglycaemia-induced reduction in complex III content and activity.

Answer 8

Imeglimin

Question 9

PPAR-gamma can be activated directly by ….. which increase PGC1alpha expression and upregulate mitochondrial biogenesis.

Answer 9

Pioglitazone

Question 10

Name drug that alter mitochondrial biogenesis.

Answer 10

Pioglitazone metabolite (Leriglitazone)
AMPK activator PXL770

Question 11

Name a drug which alters mitohcondrial function to induce apoptosis.

Answer 11

Venetoclax

Question 12

Name a drug which alters mitohcondrial signalling - redox state.

Answer 12

Sonlicromanol

Question 13

Which system does sonlicromanol target?

Answer 13

Novel antioxidant agent targeting the Trx system

Question 14

Which drug targets maternally inherited diabetes and deafness (MIDD)?

Answer 14

Sonlicromanol

Question 15

How do you replenish NAD+ stocks?

Answer 15

nicotinamide

Question 16

Which drug has received fast track and orphan drug designation by FDA in US and is under review by EMA for treatment of DMD patients who are not using glucocorticoids and which category of drug is it?

Answer 16

Idebenone

Question 17

Which drug has been developed for Non-alcoholic steatohepatitis (NASH) and what does it inhibit?

Answer 17

PPAR-y-sparing glitazone derivatives (MSDC-0602K)
AMPK activator PXL770 is also in development (phase 2) for NASH
Mitochondrial pyruvate carrier