Chapter 9: Mitochondrial Structure and Function - Constriction is completed via soluble proteins
Introduction (Drp1 in mammals) from the cytosol
2 Billion years ago: - Fusion-fission balance majorly determines - Early earth atmosphere consisted of molecular mitochondrial number, length, and degree of hydrogen (H2), ammonia (NH3) and H2O. interconnection - Anaerobes – organisms that captured and - Fusion > fission : mitochondria more elongated utilized energy by oxygen-independent and interconnected metabolisms such as fermentation and glycolysis - Fusion < fission : mitochondria more numerous 2.4-2.7 Billion years ago: and distinct - Cyanobacteria – carried out photosynthetic - Neurologic diseases can be caused by genetic process where water molecules were split and mutations that encode components of the fusion O2 was released. machinery of mitochondria - After cyanobacteria, Earth’s atmosphere began Predominance of Mitochondria in Animals to show significant levels of oxygen - 15-20 % of volume of average mammalian liver - This lead to a dramatic change in the organisms cell, contains more than 1000 diff. proteins that lived on earth - Role in generating ATP: mitochondria associates Molecular Oxygen (O2) with fatty acids (w/ oil droplets) from which the - Potentially a very toxic substance raw materials that will be oxidized come from - Takes on extra electrons and can react with a - In sperm, mitochondria are arranged in the variety of biological molecules midpiece just behind the nucleus. (Movements - Was a powerful agent for natural selection of sperm are powered by ATP from - Species evolved to protect from the damaging mitochondria) effects of O2 and also harness the molecule via Predominance of Mitochondria in Plants metabolic pathways - They are the primary suppliers of ATP in non- - Organisms that incorporated O2 could photosynthetic tissues completely oxidize compounds such as lactic acid - Source of ATP during dark periods when and ethanol into CO2 and H2O, extracting a larger photosynthesis cannot take place percentage of energy content from their food Other functions of the Mitochondria Aerobes - Sites of synthesis of numerous substances - Organisms dependent of oxygen including some amino acids and heme groups - Eventually gave rise to all oxygen-dependent - (w/ ER) Vital role in the uptake and release of prokaryotes and eukaryotes calcium ions where they regulate the Ca2+ Mitochondria concentration in the cytosol - Found in eukaryotes - Ca2+ transporters in the inner mitochondrial - A specialized organelle where the utilization of membrane takes up excess Ca2+ ions when levels oxygen as a means of energy extraction takes of calcium are abnormally high in the cytosol place - Cell death is regulated by mitochondrial events - Evolved from ancient aerobic bacterium that Mitochondrial Membranes resided in the cytoplasm of an anaerobic host - Two membranes: Outer mitochondrial 9.1 Mitochondrial Structure and Function membrane (OMM) and Inner mitochondrial Observing the Mitochondria membrane (IMM) - Can be seen in the light microscope Outer Mitochondrial Membrane: - Can appear as individual bean shaped organelles - Completely encloses mitochondrial (1-4um in length) - Serves as outer boundary - Can also appear as a highly branched, - Composed of ≈ 50 % lipid by weight + a mixture interconnected tubular network of enzymes involved in oxidation of epinephrine, - Fluorescently labelled mitochondria have been degradation of tryptophan, and elongation of observed to be dynamic organelles capable of fatty acids dramatic changes in shape - Thought to be homologous to an outer - Can fuse with one another, or can be split into membrane as part of a cell wall in gram-negative two bacteria because they both contain porins Mitochondria and the ER - Porins: - Engages in extensive interactions o integral proteins with large inner - Mitochondrial fission induced by thin tubules of channels ER o not static structures and can reversibly - ER tubules encircle mitochondria like a noose close in response to intracellular and initiate constriction conditions o Channels open: outer membrane is - mtRNA polymerase is similar to single subunit freely permeable to ATP, NAD, and enzyme in bacteriophages coenzyme A (energy metabolism) 9.2 Oxidative Metabolism in the Mitochondria Inner Mitochondrial Membrane: Oxidation of Carbohydrates: - Consists of >100 different polypeptides - Begins with glucose, carried out by enzymes of - Has a high protein to lipid ratio (more than 3:1 glycolysis in the cytosol by weight or 1 protein to every 15 phospholipid) - Only a small fraction of free energy is available - Practically without cholesterol, and rich in to the cell during glycolysis (net synthesis: 2 ATP) cardiolipin (diphosphatidylglycerol) - Most energy remains in pyruvate - Cardiolipin: Facilitates activities of large protein - Two products of glycolysis: pyruvate and NADH complexes in electron transport and ATP can be metabolized depending on the type of synthesis cell, and the presence or absence of oxygen - Highly impermeable, molecules require special Key Steps of Glycolysis: membrane transporters to enter the matrix 1. Phosphorylation of glucose to fructose - Bilayer fluidity facilitate interaction of ATP phosphate (-1 ATP) formation components 2. Phosphorylation of fructose phosphate to form - Subdivided into two major domains which have Fructose 1,6-bis-phosphate (-1 ATP) distinct functions and different protein residents 3. Fructose 1,6-bis-phosphate (six-carbon 1. Inner Boundary Membrane bisphosphate) is split into Glyceraldehyde 3- o Just inside the OMM phosphate (three-carbon monophosphate) o Forms a double-membrane outer 4. Glyceraldehyde 3-phosphate is oxidized to an envelope acid, electrons are removed and used to reduce o Rich with proteins in charge of import NAD+ to NADH. Carbon-1 acid is phosphorylated of mitochondrial proteins to form the acyl phosphate found in 1,3- 2. Cristae bisphosphoglycerate o Invaginated membranous sheets 5. C1 phosphate group from 1,3- o Energy transducers bisphosphoglycerate is transferred to ADP o Contain a large amount of membrane forming ATP via substrate-level phosphorylation, surface that houses the machinery forming 3-phosphoglycerrate (+2 ATP) needed for aerobic respiration and ATP 6. 3-phosphoglycerate undergoes rearrangement formation and dehydration forming an enol phosphate at - Cristae and Inner Boundary Membrane are the C2 atom of Phosphoenol-pyruvate joined by cristae junctions 7. Phosphate group of phsophoenol-pyruvate is - Matrix: Aqueous compartment in the interior of transferred to ADP via substrate-level the mitochondrion, has a gel-like consistency phosphorylation, generating a ketone at C2 due to the presence of high conc (<500 mg/ml) position of Pyruvate (+2 ATP) of water soluble proteins Aerobic respiration: - Intermembrane space: Aqueous compartment - In the presence of O2, can extract large amounts between OMM and IMM, proteins here initiate of additional energy from the two products cell suicide (enough to synthesize 30 more ATP) The Mitochondrial Matrix - Extracted in mitochondria - Contains ribosomes (smaller than cytosol - Pyruvate is transported into the matrix and is ribosomes), and several molecules of (circular in decarboxylated to from two-carbon acetyl group higher plants and animals) DNA which is transferred to coenzyme A to produce - Possess their own genetic material, and acetyl CoA (all catalyzed by pyruvate manufactures their own RNA and proteins dehydrogenase) - Non-chromosomal DNA encodes mitochondrial The Tricarboxylic Acid (TCA) Cycle AKA Krebs Cycle polypeptides (13 in humans) which are tightly - Acetyl CoA is fed into a cyclic pathway where the integrated into the IMM with nuclear substrate is oxidized and energy is conserved polypeptides - Aside from succinate dehydrogenase (bound to - Human mitochondrial DNA (mtDNA) encodes 2 the IMM), all other enzymes reside in the soluble ribosomal RNAs and 22 tRNAs (for protein phase of the matrix synthesis) 1. Condensation of Acetyl CoA (2 C) with - Genes from ancestor left to encode most Oxaloacetate (4 C) to form Citrate (6 C) hydrophobic proteins of IMM 2. Citrate (6 C) is converted to Isocitrate (6 C) via - RNA polymerase that synthesizes mtRNA is not Aconitase related to the multi-subunit enzyme found in prokaryotes and eukaryotes 3. Isocitrate (6 C) is converted to α-Ketoglutarate (5 C) by Isocitrate dehydrogenase (NAD+ to NADH + H+, CO2 is released) 4. Α-Ketoglutarate (5 C) is converted to Succinyl- CoA (4 C) by α-Ketoglutarate dehydrogenase (NAD+ to NADH + H+, HS-CoA is added, CO2 released) 5. Succinyl-CoA (4 C) is converted to Succinate (4 C) by Succinyl-CoA synthase (GDP + Pi to GTP, HS- CoA is released) 6. Succinate (4 C) is converted to Fumarate (4 C) by succinate dehydrogenase (FAD to FADH2) 7. Fumarate (4 C) is converted to Malate (4 C) by fumarase (H2O is added) 8. Malate (4 C) is converted back to Oxaloacetate (4 C) by Malate dehydrogenase (NAD+ to NADH + H +) - The citrate molecule is decreased in chain length, one carbon at a time to form back to oxaloacetate - 2 carbons are removed and completely oxidized into CO2 - Four reduction reactions (3, 4, 6, 8) occur where a pair of electrons are transferred to an electron accepting coenzyme - Net Equation: Acetyl CoA + 2 H2O + FAD + 3 NAD+ + GDP + Pi -> 2 CO2 + FADH2 + 3 NADH + 3 H+ + GTP + HS-CoA - Metabolites of the TCA cycle are the same compounds generated by most of the cell’s catabolic pathways HAHAHAHAHA I DON’T NEED TO DO THIS ANYMORE