NOX4 in Mitochondria: Yeast Two-Hybrid-Based Interaction with Complex I Without Relevance for Basal Reactive Oxygen Species?

Christine Hirschhaeuser, Julia Bornbaum, Anna Reis, Sabrina Boehme, Nina Kaludercic, Roberta Menabo, Fabio Di Lisa, Kerstin Boengler, Ajay M. Shah, Rainer Schulz, Harald H. H. W. Schmidt*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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NADPH oxidases (NOXs) represent the only known dedicated source of reactive oxygen species (ROS) and thus a prime therapeutic target. Type 4 NOX is unique as it produces H2O2, is constitutively active, and has been suggested to localize to cardiac mitochondria, thus possibly linking mitochondrial and NOX-derived ROS formation. The aim of this study was to identify NOX4-binding proteins and examine the possible physiological localization of NOX4 to mitochondria and its impact on mitochondrial ROS formation. We here provide evidence that NOX4 can, in principle, enter protein-protein interactions with mitochondrial complex I NADH dehydrogenase subunits, 1 and 4L. However, under physiological conditions, NOX4 protein was neither detectable in the kidney nor in cardiomyocyte mitochondria. The NOX inhibitor, GKT136901, slightly reduced ROS formation in cardiomyocyte mitochondria, but this effect was observed in both wild-type and Nox4(-/-) mice. NOX4 may thus associate with mitochondrial complex I proteins, but in cardiac and renal mitochondria under basal conditions, expression is beyond our detection limits and does not contribute to ROS formation. Antioxid. Redox Signal. 23, 1106-1112.
Original languageEnglish
Pages (from-to)1106-1112
JournalAntioxidants & Redox Signaling
Issue number14
Publication statusPublished - 10 Nov 2015

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