Mitochondria Flashcards
- Describe the origin, basic structure and fission/fusion of mitochondria.
-Origin of mitochondria believed to have happened via endocytosis of bacteria capable of oxidative phosphorylation –> Endosymbiont Hypothesis.
(remember freshmen year bio dillon… Remember dammit.)
-Would explain why mitochondria has 2 membranes. -Thus the IMM–> bacterial origin.
-The OMM –> euk org.
- Leaky OMM –>very tightly regulated
- IMM (contains most of the machinery required for oxidative phosphorylation; surface area increased by cristae) –> matrix (where mtDNA is located).
-Fusion = plays a role in repairing damaged mitochondria in that it allows bad mt to fuse with a good mt –>requires GTPase Mfn and OPA1.
To Remember:
“If I eat enough Mfn(s) ill do a Fusion and turn in to that korean guy from gangnam style” “OPA1!!!”
-Fission is required for mitophagy (degradation of bad mt) and relies on GTPase Fis1 and Drp.
“Fission for Fis1 is for Drps”
- Describe the basic machinery of mitochondria import.
- Mitochondria has its own DNA in the matrix and encodes a lot of enzymes necessary for oxidative phosphorylation.
- But still, a lot of necessary mt proteins come from nuclear DNA and so they have to be targeted/transported to mt matrix while still preserving the integrity of the IMM –> use TIMs and TOMs.
- TOM40 = huge pore in the OMM -> non-gated, always open (which is why the OMM is so leaky).
- Proteins with mitochondrial targeting sequences are recognized by TOM20 and GIP –> can cross the OMM. -Only passive transport happens here.
- To cross the IMM –> use the TIM23 complex
- (TIM22 to become part of IMM).
- TIMs are gated channels that are always closed unless the protein has a signal sequence –>opens briefly to prevent H+ from leaking (ATP-dependent process).
- Proteins can’t fit in the IMM when folded, so mtHsp70 helps them denature before entering by ‘yanking’ them through the pore.
(what i got from this, TOM is an adult so he lives by himself on the outside passively. TIM is still a kid, and requires a lot of work (ATP-dependent) so he lives on the inside so he can be closer to the DNA his mother gave him. and then mtHsp70 doesnt help fold like you would think it actually denatures.
- State the basic principles of electron transport and ATP production in mitochondria.
- Glycolysis happens in the cytosol (no oxygen required) –> 6-C glucose gets broken down into two 3-C pyruvates –> generates 2 ATP and 2 NADH.
- Pyruvates can build up as lactic acid or undergo fermentation.
- In oxidative phosphorylation in the mitochondria, you get a whole lot more ATP.
- citric acid cycle degrades pyruvate = 4 NADH, 1 FADH which go to the ECT (consists of 4 enzymes).
- NADH gets oxidized, releases its protons, which gets pumped out, and electrons are passed along the enzymes.
- Get 3 protons pumped across IMM, and 2 protons used to make H2O to neutralize electrons.
- Proton gradient is established –> we can’t have a leaky IMM or all this work is for nothing.
- ATP Synthase uses the proton gradient –> H+ fluxes through the channel and provides the energy to make ATP.
- 3H+ = one ATP molecule
- ATP synthase has an F0 complex (spans the IMM and forms the proton channel) and
- F1 complex (bound to F0 and is the enzyme that actually makes ATP).
- ATP synthase actually acts like a motor –> hexamers with a shaft to keep it in place and it spins to make ATP.
- 3 conformational changes:
1) enzyme binds ADP + Pi.
2) brings them together –> ATP.
3) Decrease in ATP affinity so it can release it. - ATP transported out of mitochondria via an ATP-ADP antiporter.
- Explain the basic mechanisms of cell death regulation by mitochondria.
- Defective mt’s are leaky, can signal apoptosis.
- Cell damage –> Bak/Bax-dependent perforation of the OMM –> cytochrome C release –> binds to cytoplasmic proteins that activates the formation of an apoptosome –> activates caspases that cause apoptosis. BUT even if this is under way, you can oxidize cyt c and stop the process, true for necrosis too. cool right.
- In ischemic injury, mitochondria can promote necrotic cell death by causing MPTP-dependent perforation of OMM and IMM. –>cytochrome release and elimination of proton gradient.
- No ATP can be produced so the whole cell is going to die.
- Also causes ATP synthase to become ATPase –>uses up any available ATP.
- If we can control this response, we can maybe control ischemic injury.
-Important response because bad mt can cause too much ROS to be present –> cell damage and senescence because it is highly reactive and will oxidize whatever it comes into contact with.
- State the principles of mitochondria quality control.
Three levels of regulation for these bitch ass culeros:
1) -Proteolytic cleavage –> mt has proteases that degrade proteins in the matrix if they’re not working properly.
- (So the three mt proteases that recognize and degrade misfolded proteins are mAA, iAAA, & Lon.)
- OMM proteins degraded by a normal proteasome.
- mAAA degrades defective proteins in the IMS (?).
- iAAA is another protease that recognizes/degrades bad proteins.
- Lon is in the matrix and degrade misfolded proteins there.
2) -If you have too much protein –> can undergo fusion to dilute it out. In this process damaged mitochondria can be “fixed”by fusing with healthy mitochondria OR can be eliminated by mitophagy.
- Mitophagy = specialized to degrade defective mitochondria and transport to lysosome.
3)-if mt too fucked up–> apoptosis
- Describe the role of mitochondria in senescence and some of the mitochondria-related diseases.
- Accumulation of ROS –> senescence and increased sensitivity to neuronal degeneration.
- Several mutations in the mitochondria quality control pathways result in various neuropathies
- Mutations in fusion gene OPA1 causes autosomal dominant optic atrophy and mutations
- Mutations in Mfn2 gene –> CMT type 2A.
- Mutation in mAAA protease = hereditary spastic paraplegia.
- Arsenic inhibits oxidative phosphorylation by inhibiting ATP production.
