title: Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria.
abstract: Mycobacteria inhabit a wide range of intracellular and extracellular environments. Many of these environments are highly dynamic and therefore mycobacteria are faced with the constant challenge of redirecting their metabolic activity to be commensurate with either replicative growth or a non-replicative quiescence. A fundamental feature in this adaptation is the ability of mycobacteria to respire, regenerate reducing equivalents and generate ATP via oxidative phosphorylation. Mycobacteria harbor multiple primary dehydrogenases to fuel the electron transport chain and two terminal respiratory oxidases, an aa3 -type cytochrome c oxidase and cytochrome bd-type menaquinol oxidase, are present for dioxygen reduction coupled to the generation of a protonmotive force. Hypoxia leads to the downregulation of key respiratory complexes, but the molecular mechanisms regulating this expression are unknown. Despite being obligate aerobes, mycobacteria have the ability to metabolize in the absence of oxygen and a number of reductases are present to facilitate the turnover of reducing equivalents under these conditions (e.g. nitrate reductase, succinate dehydrogenase/fumarate reductase). Hydrogenases and ferredoxins are also present in the genomes of mycobacteria suggesting the ability of these bacteria to adapt to an anaerobic-type of metabolism in the absence of oxygen. ATP synthesis by the membrane-bound F1FO-ATP synthase is essential for growing and non-growing mycobacteria and the enzyme is able to function over a wide range of protonmotive force values (aerobic to hypoxic). The discovery of lead compounds that target respiration and oxidative phosphorylation in Mycobacterium tuberculosis highlights the importance of this area for the generation of new front line drugs to combat tuberculosis.
authors.affiliation: University of Otago, Department of Microbiology and Immunology, Dunedin, New Zealand.
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Cook
authors.affiliation: University of Otago, Department of Microbiology and Immunology, Dunedin, New Zealand.
authors.forename: Kiel
authors.initials: K
authors.lastname: Hards
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461.
authors.forename: Catherine
authors.initials: C
authors.lastname: Vilchèze
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461.
authors.forename: Travis
authors.initials: T
authors.lastname: Hartman
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461.
authors.forename: Michael
authors.initials: M
authors.lastname: Berney
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000332:Aerobiosis; D004734:Energy Metabolism; D053858:Metabolic Networks and Pathways; D009169:Mycobacterium tuberculosis / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D010088:Oxidoreductases / Q000378:metabolism
chemical_list: D000255:Adenosine Triphosphate; D010088:Oxidoreductases