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Sci. Signal., 28 January 2014
Vol. 7, Issue 310, p. ra10
[DOI: 10.1126/scisignal.2004374]

RESEARCH ARTICLES

ROMO1 Is an Essential Redox-Dependent Regulator of Mitochondrial Dynamics

Matthew Norton1,2, Andy Cheuk-Him Ng1,3, Stephen Baird1, Ariane Dumoulin1, Timothy Shutt4, Nancy Mah5, Miguel A. Andrade-Navarro5, Heidi M. McBride6, and Robert A. Screaton1,2,7*

1 Children’s Hospital of Eastern Ontario Research Institute, 401 Smyth Road, Ottawa, Ontario K1H 8L1, Canada.
2 Department of Cellular and Molecular Medicine, University of Ottawa, 501 Smyth Road, Ottawa, Ontario K1H 8M5, Canada.
3 Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada.
4 University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, Ontario K1Y 4W7, Canada.
5 Max Delbrück Center for Molecular Medicine, Robert-Rössle-Str. 10, 13125 Berlin, Germany.
6 Montreal Neurological Institute, 3801 University Avenue, Montreal, Quebec H3A 2B4, Canada.
7 Department of Pediatrics, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada.

Abstract: The dynamics of mitochondria undergoing fusion and fragmentation govern many mitochondrial functions, including the regulation of cell survival. Although the machinery that catalyzes fusion and fragmentation has been well described, less is known about the signaling components that regulate these phenomena. We performed a genome-wide RNA interference (RNAi) screen and identified reactive oxygen species modulator 1 (ROMO1) as a redox-regulated protein required for mitochondrial fusion and normal cristae morphology. We showed that oxidative stress promoted the formation of high–molecular weight ROMO1 complexes and that knockdown of ROMO1 promoted mitochondrial fission. ROMO1 was essential for the oligomerization of the inner membrane guanosine triphosphatase (GTPase) OPA1, which is required to maintain the integrity of cristae junctions. As a consequence, cells lacking ROMO1 displayed fragmented mitochondria and loss of cristae, causing impaired mitochondrial respiration and increased sensitivity to cell death stimuli. Together, our data identify ROMO1 as a critical molecular switch that couples metabolic stress and mitochondrial morphology, linking mitochondrial fusion to cell survival.

* Corresponding author. E-mail: rob{at}arc.cheo.ca

Citation: M. Norton, A. C.-H. Ng, S. Baird, A. Dumoulin, T. Shutt, N. Mah, M. A. Andrade-Navarro, H. M. McBride, R. A. Screaton, ROMO1 Is an Essential Redox-Dependent Regulator of Mitochondrial Dynamics. Sci. Signal. 7, ra10 (2014).

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