title: Nitric oxide-associated protein 1 (NOA1) is necessary for oxygen-dependent regulation of mitochondrial respiratory complexes.
abstract: In eukaryotic cells, maintenance of cellular ATP stores depends mainly on mitochondrial oxidative phosphorylation (OXPHOS), which in turn requires sufficient cellular oxygenation. The crucial role of proper oxygenation for cellular viability is reflected by involvement of several mechanisms, which sense hypoxia and regulate activities of respiratory complexes according to available oxygen concentrations. Here, we focus on mouse nitric oxide-associated protein 1 (mNOA1), which has been identified as an important component of the machinery that adjusts OXPHOS activity to oxygen concentrations. mNOA1 is an evolutionary conserved GTP-binding protein that is involved in the regulation of mitochondrial protein translation and respiration. We found that mNOA1 is located mostly in the mitochondrial matrix from where it interacts with several high molecular mass complexes, most notably with the complex IV of the respiratory chain and the prohibitin complex. Knock-down of mNOA1 impaired enzyme activity I+III, resulting in oxidative stress and eventually cell death. mNOA1 is transcriptionally regulated in an oxygen-sensitive manner. We propose that oxygen-dependent regulation of mNOA1 is instrumental to adjusting OXPHOS activity to oxygen availability, thereby controlling mitochondrial metabolism.
authors.affiliation: Department of Cardiac Development and Remodeling, Max-Planck-Institute for Heart and Lung Research, Ludwigstrasse 43, 61231 Bad Nauheim, Germany.
authors.forename: Juliana
authors.initials: J
authors.lastname: Heidler
authors.forename: Natalie
authors.initials: N
authors.lastname: Al-Furoukh
authors.forename: Christian
authors.initials: C
authors.lastname: Kukat
authors.forename: Isabelle
authors.initials: I
authors.lastname: Salwig
authors.forename: Marie-Elisabeth
authors.initials: ME
authors.lastname: Ingelmann
authors.forename: Peter
authors.initials: P
authors.lastname: Seibel
authors.forename: Marcus
authors.initials: M
authors.lastname: Krüger
authors.forename: Jürgen
authors.initials: J
authors.lastname: Holtz
authors.forename: Ilka
authors.initials: I
authors.lastname: Wittig
authors.forename: Thomas
authors.initials: T
authors.lastname: Braun
authors.forename: Marten
authors.initials: M
authors.lastname: Szibor
mesh_terms: D000818:Animals; D004579:Electron Transport / Q000502:physiology; D042967:Electron Transport Complex I / Q000235:genetics / Q000378:metabolism*; D003576:Electron Transport Complex IV / Q000235:genetics / Q000378:metabolism*; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D041681:NIH 3T3 Cells; D010085:Oxidative Phosphorylation; D010100:Oxygen / Q000378:metabolism*; D010101:Oxygen Consumption / Q000502:physiology
chemical_list: D024101:Mitochondrial Proteins; D003576:Electron Transport Complex IV; D020558:GTP Phosphohydrolases; C559566:NOA1 protein, mouse; D042967:Electron Transport Complex I; D010100:Oxygen