Mitochondria & cell death pathways Flashcards

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1
Q

Facts about mitochondria?

A

1um length

10-1000 per cell

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2
Q

What is the mitochondrial matrix?

A

concentrated enzymes for oxidation of pyruvate & fatty acids (citric acid cycle)

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3
Q

What is the mitochondrial inner membrane?

A

folded into cristae
contains proteins - oxidation reactions of ETC
contains ATP synthase

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4
Q

What is the mitochondrial outer membrane?

A

contains porin - permeables to molecules <5000daltons

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5
Q

What is the mitochondrial intermembrane space?

A

contains enzymes that use ATP to phosphorylate other nucleotides

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6
Q

Whate does the citric acid cycle produce?

A

NADH

carbon dioxide

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7
Q

What are the 2 main classes of food molecules?

A

pyruvate - sugars from glycolysis

fatty acids - from storage & diet

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8
Q

What happens to food molecules when taken into matrix?

A

produce acetyl CoA
oxidised in citric acid cycle
produce NADH & CO2
electrons from NADH travel along ETC

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9
Q

What is ‘coupled’ in the mitochondria?

A

NADH oxidation & ATP synthesis

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10
Q

What are the 3 main protein complexes involved int he ETC?

A

NADH dehydrogenase complex

cytochrome b-c1 complex

cytochrome oxidase complex

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11
Q

What are the 2 diff molecules involved in passing electrons to complexes in the ETC?

A

ubiquinone (Q) - complex 1 -> 2

cytochrome c (c) complex 2 -> 3

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12
Q

What are the gradients in the inner mitochondrial membrane?

A

pH & voltage gradients

allows protons to cross membrane and create energy

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13
Q

Where is ATP synthase located?

A

embedded in membrane

protrudes into matrix

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14
Q

What is mtDNA?

A

2-10 copies of closed, circular dsDNA
maternally inherited
needs proteins encoded by nuclear genome

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15
Q

What is the size of human mtDNA?

A

17kb genome

small compared to yeast

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16
Q

What does mtDNA code for?

A

tRNAs
can make own ribosomes
subunits of cytochrome c oxidase

17
Q

What are mitochondrial diseases?

A

maternally inherited
high mutation rates compared to DNA
neuromuscular disease
tendency to divide and move to state of homoplasmy

18
Q

What are 3 examples of mtiochondrial disease?

A

Leber’s hereditary optic neuropathy (LHON)

Kearn-Sayers syndrome (KSS)

Ragged muscle fibre syndrome

19
Q

What is a way to treat mitochondrial diseases?

A

3 person IVF

20
Q

What is apoptosis?

A

cell death in a controlled manner that follows a defined programme - DOES NOT provoke immune response

plasma membrane reorganised into blebs

21
Q

What is the extracellular pathway of apoptosis?

A

activation of death receptors on cell surface

22
Q

What is the intracellular pathway of apoptosis?

A

withdrawal of survival factors = DNA damage, metabolic stress, hypoxia

23
Q

What do extracellular and intracellular pathways of apoptosis lead to?

A

activation of an intracellular proteolysis system mediated by capsases

24
Q

how does procapsase activation by cleavage occur?

A

remove pro domains

form multi-subunit enzymes

25
Q

What is the amplifying capsase cascade?

A

once 1 molecule is produced it can cleave others

2 classes of capsases - initiator capsases & executional capsases

26
Q

What is an activator of the amplification system?

A

cytochrome C

outer membrane leaky - cyt c spill out - binds to adaptor protein that forms macromolecular assembly

recruitment of procapsase-9

activation of procapsase-9 within apoptosome

27
Q

What is the Bcl-2 family?

A

anti-apoptotic
found in B Cell Lymphomas
25kDa
Homolgoues such as Bax form heterodimers with Bcl-2 = inactivation

28
Q

How is apoptosis blocked by survival factors?

A

activate receptor

activated transcription regulator - upregulation of anti-apoptotic Bcl-2

29
Q

What does adenovirus E1B-19kDa protein form?

A

complex with Bax family - suppresses release of cyt c via mitochondrial pores

(also happens in herpes)