ROMO1 is an essential redox-dependent regulator of mitochondrial dynamics.
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.
1Children's Hospital of Eastern Ontario Research Institute, 401 Smyth Road, Ottawa, Ontario K1H 8L1, Canada.
Matthew
M
Norton
Andy Cheuk-Him
AC
Ng
Stephen
S
Baird
Ariane
A
Dumoulin
Timothy
T
Shutt
Nancy
N
Mah
Miguel A
MA
Andrade-Navarro
Heidi M
HM
McBride
Robert A
RA
Screaton
D002470:Cell Survival / Q000502:physiology; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D055106:Genome-Wide Association Study; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D010101:Oxygen Consumption / Q000502:physiology*; D034622:RNA Interference
D008565:Membrane Proteins; D024101:Mitochondrial Proteins; C513338:ROMO1 protein, human; D020558:GTP Phosphohydrolases; C415198:OPA1 protein, human