Nitric oxide-associated protein 1 (NOA1) is necessary for oxygen-dependent regulation of mitochondrial respiratory complexes

Juliana Heidler, Natalie Al-Furoukh, Christian Kukat, Isabelle Salwig, Marie Elisabeth Ingelmann, Peter Seibel, Marcus Krug̈er, Jur̈gen Holtz, Ilka Wittig, Thomas Braun, Marten Szibor

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

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. mNOA1is an evolutionary conserved GTP-binding protein that is involved in the regulation of mitochondrial protein translation and respiration.Wefound thatmNOA1is 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. Knockdown 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.

Original languageEnglish
Pages (from-to)32086-32093
Number of pages8
JournalJournal of Biological Chemistry
Volume286
Issue number37
DOIs
StatePublished - 16 Sep 2011
Externally publishedYes

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