The outer mitochondrial membrane is permeable to most
molecules. The inner mitochondria membrane is impermeable to most molecules including pyruvate, CoA, NADH but permeable to O2, CO2, H2O and ammonia. The mtDNA encodes rRNA, tRNA and some proteins for ox-phos. Reducing equivalents are shuttled into the mitochondria by the Malate-aspartate shuttle and the glycerol-3-phosphate shuttle (ubiquinone) NADH is the primary donor of hydrogens and electons. O2 is the final electron acceptor. STAT3 protects against Ischemia-induced changes in the Electron Transport Chain and the generation of reactive oxygen species. The mitochondrial electron transport is downregulated during myocardia ischemia to prevent the production of reactive oxygen species.
Mitochondrial Electron Transport System
Electron Flow: Complex I + Complex II CoQ Complex III Cytochrome c Complex IV Complex I, III and IV produce H.
Components of Electron Tranport Chain
Complex I NADH Dehydrogenase
Transfers 2H and 2 electrons to CoQ by FMN and Fe-S centers.
Pumps 4 protons into intermembrane space. NAD carries 2 electrons and 1 H on the nicotimide ring. FMN carries 2 electrons and 2 H on the isoalloxazine ring. A flavin linked enzyme.
Iron-Sulfur Proteins
Non-heme iron proteins.
Contain Fe and sulfur. Found on Complex I, II, III Carry one electron at a time. Ubiquitous
Complex II Succinate Dehydrogenase
Part of Krebs cycle.
Succinate donate 2 H and 2 electrons to FAD. Fe-S centers pass electrons to CoQ. No proton transported.
Coenzyme Q
Carries 2 H, 2 electrons in benzoquinone ring.
Soluble in lipid membrane due to long hydrophobic side chain.
Heme and Cytochromes
Found in all cytochromes, hemoglobin and myoblobin.
Made from succinyl-CoA in the Krebs cycle. CO can bind to hemoglobin.
Complex III Cytochrome b-c1
Heme iron plus protoporphyrin ring.
Pumps 4 H into intermembrane space. 2 CoQ binding sites. CoQ donates electrons to Cyt bc1 one at a time.
Cytochrome C
Transfers electrons between complexes III and IV.
Contains heme c. Involved in apoptosis. MOMP mitochondrial outer membrane permeabilization.
Complex IV cytochrome c oxidase
Contains heme A and 2 copper ions.
Accepts 4 electrons from cytochrome c and 4 hydrogens from matrix. Reduce O2 to H2O Pumps 4 protons to IM space. Poisoned by cyanide.
Mitchell came up with the Chemiosmotic Hypothesis of ATP synthesis.
ATP Synthase
ATP synthesis is driven by H gradient.
Central gamma subunit rotates due to gradient. ATP synthesis catalyzed by beta subunits. C subunit and alpha subunits hold beta subunits stationary. ATP is exchanged with ADP in the intermembrane space by AAC to replenish ADP supplies.