Term
| How do compounds move in and out of the outer mitochondrial membrane? |
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Definition
1) ATP,ADP, pyruvate- porins.
2) cytoplasmic protein uptake- TOM complex
3) Cholesterol uptake
4) Mitochondrial Permeability Transition Pore
a. Voltage-dependent anion channel (VDAC)
b. Cyclophilin D |
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Term
| What major protein complexes exist in the inner mitochondrial membrane? |
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Definition
1) ETC
2) ATP Synthase (F-type ATPase)
3) Metabolite-specific carrier proteins
4) Adenine Nucleotide Exchange Factor (ANT)- component of MPT that exchanges m-ATP for c-ADP
5) Thermogenin (ETC-uncoupler in brown fat)
6) TIM complex |
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Term
| What are the major contents of the mitochondrial matrix? |
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Definition
| 1) TCA and OXPHOS enzymes, m-DNA, tRNAs. |
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Term
| Why might mitochondria in steroid-secreting cells have extensive inner membranes? |
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Definition
This is where steroid-producing enzymes are found!
Remember, mitochondria are dynamic and motile structures! |
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Term
| What recent clinical correlations for Cyclophillin D have been observed? |
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Definition
1) drug target to limit mitochondrial-dependent necrosis in muscular dystrophy
2) loss of Cyclophilin D in A-disease models reduces synaptic plasticity deficits. |
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Term
| What antioxidant response systems exist in mitochondria to eliminate O2- generated by the ETC? |
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Definition
1) SOD
2) Glutathione Peroxidase
3) Catalase |
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Term
1) What is the difference b/w homoplasmy and heteroplasmy?
2) Explain the relevance of the ATP6 point mutation. |
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Definition
1) Homoplasmy is the mitochondrial genotype derived from a single mtDNA
Heteroplasmy is the mitochondrial genotype derived from one mutant and one wildtype mtDNA in the same mitochondria.
2) Heteroplasmic ATP6 gene mutations (ATP synthase subunit).
When present in <75% of mtDNAs causes neurogenic muscle weakness, ataxia and retinitis pigmentosa (NARP).
When it is in >95%, Leigh's syndrome is seen, which is a rate neurodegenerative disorder that is fatal. |
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Term
| Why might you see "ragged red fibers" in a tissue biopsy? |
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Definition
| Signals mitochondrial abnormality, usually with ETC components. |
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Term
| How do proteins gain access to the intermembrane space of mitochondria? What about the mitochondrial matrix? |
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Definition
1) To pass through OM, TOM receptors must recognize N-terminal signal patch (positively charged alpha helix) on translocating protein (post-translational translocation- proteins are in UNFOLDED state).
2) To pass through the IM, proteins must interact with the TIM complex at either TIM23 (inner-membrane protein), TIM22 (to matrix) or OXA (from matrix back to IM or IM-space) |
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Term
| What are 3 sources of energy that drive mitochondrial protein import? |
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Definition
1) Cytoplasmic hsp70 (presents unfolded protein to TOM, released by ATP exchange)
2) Proton motive force (IM-space proton gradient)
3) Mitochondrial hsp70 and hsp60 (70-binds and 60-refolds) |
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Term
| How does nuclear and mitochondrial protein importing differ? |
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Definition
Nuclear- in folded state! Peroxisomal is the same!
Mitochondrial- unfolded state! |
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Term
True:False
Peroxisomes do not contain their own DNA and contain a large amount of the enzyme, catalase. |
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Definition
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Term
| Peroxisomes in the liver and kidney produce hydrogen peroxide from ROS. What role does catalase play? |
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Definition
| utilizes peroxide to oxidize other substrates (alcohols, phenols, formic acid, formaldehyde) |
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Term
| What is the major difference b/w mitochondrial and peroxisomal fat oxidation? |
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Definition
Mitochondrial- Coupled to ATP-production
Peroxisomal- Produces Heat |
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Term
| Where are plasmalogens found and what is their primary function? |
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Definition
Phospholipids synthesized in peroxisomes.
Concentrated in myelin sheath of nerves- peroxisomal disease have abnormal myelination |
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Term
1) Where are all peroxisomal proteins synthesized?
2) How do they gain access to peroxisomes? |
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Definition
1) Cell cytoplasm
2) Translocated in folded state via PTS1 (S-K-L sequence binds Pex5p) and PTS2 (9 basic AA binds Pex7p)
PTS1 is the major pathway |
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Term
| How do lipids get into peroxisomes? |
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Definition
| Same as with mitochondria: single-molecule carriers from SER! |
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Term
| The accumulation of what types of molecule is most often associated with Peroxisomal diseases? |
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Definition
| long-chain fatty acid accumulation- affecting membrane structure and function, especially in RBCs (can cause demyelinization in brain) |
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Term
A patient presents with dysmorphic facial features, wide-set eyes and low-set ears, with deformed limbs and joints and calcium deposits in the cartilage. There is also a myelination abnormality and retinopathy.
What peroxisomal disease might this be and what is the cause? |
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Definition
Zellweger- peroxisomes are empty because of a defect in Pex5P.
Remember, this is the receptor necessary for PTS1-presenting proteins to gain access to peroxisomes!. |
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Term
| You diagnose a patient with Neonatal Adrenoleukodystrophy (NALD) and suggest trying "Lorenzo's Oil," because no other adequate therapies exist. What is the cause of this condition? |
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Definition
The patient is lacking a peroxisomal enzyme that is critical for the esterification of fatty acids to acetyl CoA.
This results in the accumulation of very long chain fatty acids in peroxisomes!
Remember you peroxisomal diseases:
Zellweger- empty peroxisomes
NALD- full of VLCFA's! |
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