BE230_Lecture_11 - Post-translational uptake of proteins by...

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Post-translational uptake of proteins by peroxisomes, mitochondria
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Protein trafficking Sorting signals Signal peptide of secreted proteins Mannose phosphate groups of lysosomal enzymes Receptors Recognise these signals and deliver protein to proper compartment Nuclei Mitochondria peroxisomes
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Uptake of proteins into Mitochondria 4 subcompartments Outer mitochondrial membrane Inner mitochondrial membrane Intermembrane space Matrix Vast majority of mitochondrial proteins are encoded by nuclear genome, synthesised in cytosol, imported posttranslationally Contain a presequence (targetting signal)
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mitochondria Large enough to be seen in light microscope 0.2-1.0 μ m diam, 1-4 μ m long 15-20% volume of liver cell OMM IMM- cristae…deep folds or invaginations House machinery for aerobic respiration Intermembrane space Matrix…rich in water soluble proteins
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OMM 50% lipid Enzymes for – oxidation of adrenaline, degradation of tryptophan, elongation of fatty acids Contain porins that open and close…ATP, NAD, CoA IMM 100 different polypeptides High protein;lipid ratio 3:1 No cholesterol Rich in cardiolipin Contain porins. .integral proteins…require special membrane transporters to gain entrance to matrix
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matrix Ribosomes Circular double stranded DNA Non chromosomal DNA encodes 13 mitochondrial polypeptides in humans Encodes 2 rRNAs 22tRNAs
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Targetting sequence Located at N terminus Positively charged amino acids Removed after protein has been imported by a mitochondrial processing protease
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Events for the preprotein Must be presented to mitochondrion in unfolded/ extended state OMM contains a protein import complex (TOM complex) Receptor that binds preproteins Protein lined channel for translocating the unfolded polypeptides into or through the OMM Proteins destined for matrix must pass thro a second barrier- IMM Occurs at sites where OMM and IMM come into close proximity IMM contains protein import complex ( TIM complex) Receptor for preprotein Channel for translocation
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Movement into matrix Powered by electric potential across IMM acting on positively charged targetting signal
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Mitochondrial chaperones Several implicated in preparing polypeptides for uptake into mitochondria mHsp70 Mediate entry to aqueous compartment Use energy derived from ATP hydrolysis to ‘pull’ unfolded proteins thro translocation pore Or Aid diffusion of polypeptide across membrane (random)
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Peroxisomes (microbodies) Simple membrane bound vesicles 0.1-1.0 um diameter Contain dense crystalline core of oxidative enzymes (~50) Oxidation of very long chain fatty acids (VLCFAs) Synthesis of plasmalogens ( PLs in brain…ether linkage instead of ester linkage) Multifunctional organelles Share several properties with mitochondria
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This note was uploaded on 01/05/2010 for the course FSH BT taught by Professor Ianmarison during the Fall '09 term at Dublin City University.

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BE230_Lecture_11 - Post-translational uptake of proteins by...

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