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ROMO1 is an essential redox-dependent regulator of mitochondrial dynamics

Item Type:Article
Title:ROMO1 is an essential redox-dependent regulator of mitochondrial dynamics
Creators Name:Norton, M., Ng, A.C., Baird, S., Dumoulin, A., Shutt, T., Mah, N., Andrade-Navarro, M.A., McBride, H.M. and Screaton, R.A.
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.
Keywords:Cell Survival, GTP Phosphohydrolases, Gene Knockdown Techniques, Genome-Wide Association Study, HeLa Cells, Membrane Proteins, Mitochondria, Mitochondrial Proteins, Oxygen Consumption, RNA Interference
Source:Science Signaling
Publisher:American Association for the Advancement of Science
Page Range:ra10
Date:28 January 2014
Official Publication:https://doi.org/10.1126/scisignal.2004374
PubMed:View item in PubMed

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