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Relationship Of Energy Functions To Cellular And Organismic Aging, Potential Role Of Dna Damage And Dna Mutations

Mitochondria are organelles found in the cytoplasm of all eukaryotic cells. They vary considerably in shape and size, but are all composed of four compartments: a smooth outer membrane, a convoluted inner membrane that forms recognizable structures called cristae, the intermembrane space, and the matrix. Mitochondria are the "powerhouses" of cells; their function is to convert energy found in nutrient molecules and store it in high-energy phosphate bonds in a molecule called adenosine triphosphate, which is the universal energy-yielding component necessary for the reactions that modulate many fundamental cellular processes. Mitochondrial ATP is produced through the process of oxidative phosphorylation, a process that uses molecular oxygen as the final electron acceptor.

The products of metabolism are carried from the cytoplasm into the mitochondrial matrix, where they go through the citric acid, or Krebs cycle. The Krebs cycle promotes the reduction of the catabolism-generated coenzymes NAD+ (nicotinamide adenine dinucleotide) and FAD (flavin adenine dinucleotide) to NADH and FADH2, respectively, which are rich in electron energy. As these molecules are reoxidized, they supply electrons that are carried to final electron acceptor via an elaborate respiratory, or electron, transport chain. The electron transport system is a chain of electron acceptors located in the inner membrane of the mitochondria.

Hydrogens are passed down from NADH to the electron transport chain in a series of redox reactions, where they become dissociated from their electrons and are released as protons. The electrons entering the electron transport system have a relatively high energy content. As they are transferred from one acceptor molecule to the next, they lose much of their energy, some of which is used to pump the protons across the inner mitochondrial membrane. This sets up an electrochemical gradient across the inner mitochondrial membrane, which provides the energy for ATP synthesis. Therefore, the function of this chain is to permit the controlled release of free energy to drive the synthesis of ATP from ADP (adenosine diphosphate, formed from the breakdown of ATP) and inorganic phosphate. This oxidative phosphorylation process engages five respiratory-chain enzyme complexes located within the inner mitochondrial membrane. Four of these complexes—I (NADH dehydrogenase), II (succinate dehydrogenase), III (cytochrome-c reductase), IV (cytochrome-c oxidase)—catalyze the transport of electrons to molecular oxygen. Complex V (ATP synthase) uses the proton motive force to form ATP from ADP and inorganic phosphate. Oxygen is the final electron acceptor in the electron transport system, which is why organisms that respire aerobically require oxygen.

Mitochondria contain their own deoxyribonucleic acid (DNA). Each human cell contains several hundred mitochondria and thousands of copies of the mitochondrial genome (mtDNA). The human mtDNA molecule is a closed circular molecule and is 16,569 base pairs (bp) in length. Out of the thirty-seven mitochondrially encoded genes, thirteen encode polypeptides that are subunits of the respiratory chain enzyme complexes; twenty-two encode transfer RNA and two encode ribosomal RNA. The twenty-four genes that encode RNA are needed for mitochondrial protein synthesis.

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Medicine EncyclopediaAging Healthy - Part 3