Lecture 4 | Mitochondrial (dys)functioning

Question 1

Mitochondrial dynamics

Answer 1

Biogenesis, fusion and fission

-> Assure mitochondrial quality

Question 2

Biogenesis + regulator(s)

Answer 2

The synthesis of new mitochondria(l proteins)
Master regulator = PGC-1a

Question 3

PGC-1a

Answer 3

Co-transcriptionfactor -> binds to PPARy (transcriptionfactor) and increases expression of mitochondrial proteins and DNA

Question 4

Ageing/ cachexia and mitochondrial biogenesis

Answer 4

Ageing: reduction in PGC-1a
Cachexia: unkown

Question 5

Fusion + regulator(s)

Answer 5

Fusion of multiple mitochondria into one mitochondria.
To mix contents and maintain respiratory capacity.
Regulators = Mfn1, Mfn2, OPA1

Question 6

Mfn1 & Mfn2

Answer 6

On outer membrane, bind to each other to ensure fusion of outer membrane

Question 7

OPA1

Answer 7

On inner membrane, ensure fusion of inner membrane

Question 8

Ageing/ cachexia and fusion

Answer 8

Both: reduction in Mfn1, Mfn2 and OPA1

Question 9

Fission + regulator(s)

Answer 9

Fission of one mitochondria into multiple mitochondria.
To split damaged parts from the mitochondria.
Regulators = Drp1

Question 10

Drp1

Answer 10

Forms ring around mitochondria to split mitochondria into functional and non-functional parts.

Question 11

Ageing/ cachexia and fission

Answer 11

Both: reduction in Drp1

Question 12

Mitophagy + regulator(s)

Answer 12

Removal of damaged mitochondria

Regulators = LC3, PINK1, P62

Question 13

Steps of mitophagy

Answer 13

1. Damaged mitochondria externalizes PINK1
2. PINK1 phophorylates Parkin
3. Parkin ubiquitinates outer mitochondrial membrane
4. P62 forms link between ubiquitin ‘antenna’ (mitochondria) and LC3 (phagophore)

Question 14

Ageing/ cachexia and mitophagy

Answer 14

Both: markers are upregulated.
However, in ageing lower mitophagy due to lysosomal dysfuntion -> no fusion of lysosome with autophagosome.
Unkown for cachexia.

Question 15

How to assess oxidative phosphorylation/ oxphos complexes

Answer 15

OROBOROS: measures oxygen usage by (permeabilized) cells or tissues.
Add different substrates (always add ADP!)