Mitochondria & cell death pathways Flashcards
Facts about mitochondria?
1um length
10-1000 per cell
What is the mitochondrial matrix?
concentrated enzymes for oxidation of pyruvate & fatty acids (citric acid cycle)
What is the mitochondrial inner membrane?
folded into cristae
contains proteins - oxidation reactions of ETC
contains ATP synthase
What is the mitochondrial outer membrane?
contains porin - permeables to molecules <5000daltons
What is the mitochondrial intermembrane space?
contains enzymes that use ATP to phosphorylate other nucleotides
Whate does the citric acid cycle produce?
NADH
carbon dioxide
What are the 2 main classes of food molecules?
pyruvate - sugars from glycolysis
fatty acids - from storage & diet
What happens to food molecules when taken into matrix?
produce acetyl CoA
oxidised in citric acid cycle
produce NADH & CO2
electrons from NADH travel along ETC
What is ‘coupled’ in the mitochondria?
NADH oxidation & ATP synthesis
What are the 3 main protein complexes involved int he ETC?
NADH dehydrogenase complex
cytochrome b-c1 complex
cytochrome oxidase complex
What are the 2 diff molecules involved in passing electrons to complexes in the ETC?
ubiquinone (Q) - complex 1 -> 2
cytochrome c (c) complex 2 -> 3
What are the gradients in the inner mitochondrial membrane?
pH & voltage gradients
allows protons to cross membrane and create energy
Where is ATP synthase located?
embedded in membrane
protrudes into matrix
What is mtDNA?
2-10 copies of closed, circular dsDNA
maternally inherited
needs proteins encoded by nuclear genome
What is the size of human mtDNA?
17kb genome
small compared to yeast
What does mtDNA code for?
tRNAs
can make own ribosomes
subunits of cytochrome c oxidase
What are mitochondrial diseases?
maternally inherited
high mutation rates compared to DNA
neuromuscular disease
tendency to divide and move to state of homoplasmy
What are 3 examples of mtiochondrial disease?
Leber’s hereditary optic neuropathy (LHON)
Kearn-Sayers syndrome (KSS)
Ragged muscle fibre syndrome
What is a way to treat mitochondrial diseases?
3 person IVF
What is apoptosis?
cell death in a controlled manner that follows a defined programme - DOES NOT provoke immune response
plasma membrane reorganised into blebs
What is the extracellular pathway of apoptosis?
activation of death receptors on cell surface
What is the intracellular pathway of apoptosis?
withdrawal of survival factors = DNA damage, metabolic stress, hypoxia
What do extracellular and intracellular pathways of apoptosis lead to?
activation of an intracellular proteolysis system mediated by capsases
how does procapsase activation by cleavage occur?
remove pro domains
form multi-subunit enzymes
What is the amplifying capsase cascade?
once 1 molecule is produced it can cleave others
2 classes of capsases - initiator capsases & executional capsases
What is an activator of the amplification system?
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
What is the Bcl-2 family?
anti-apoptotic
found in B Cell Lymphomas
25kDa
Homolgoues such as Bax form heterodimers with Bcl-2 = inactivation
How is apoptosis blocked by survival factors?
activate receptor
activated transcription regulator - upregulation of anti-apoptotic Bcl-2
What does adenovirus E1B-19kDa protein form?
complex with Bax family - suppresses release of cyt c via mitochondrial pores
(also happens in herpes)
