Opa1 relies on cristae preservation and ATP synthase to curtail reactive oxygen species accumulation in mitochondria
Rubén Quintana-Cabrera,
Israel Manjarrés-Raza,
Carlos Vicente-Gutiérrez,
Mauro Corrado,
Juan P. Bolaños,
Luca Scorrano
Affiliations
Rubén Quintana-Cabrera
Institute of Functional Biology and Genomics (IBFG), University of Salamanca, CSIC, Salamanca, Spain; Institute of Biomedical Research of Salamanca (IBSAL), University Hospital of Salamanca, University of Salamanca, CSIC, Salamanca, Spain; CIBERFES, Institute of Health Carlos III, Madrid, Spain; Department of Biochemistry and Molecular Biology, University of Salamanca, Spain; Corresponding author. Institute of Functional Biology and Genomics (IBFG), University of Salamanca, CSIC, Salamanca, Spain.
Israel Manjarrés-Raza
Institute of Functional Biology and Genomics (IBFG), University of Salamanca, CSIC, Salamanca, Spain; Institute of Biomedical Research of Salamanca (IBSAL), University Hospital of Salamanca, University of Salamanca, CSIC, Salamanca, Spain; CIBERFES, Institute of Health Carlos III, Madrid, Spain; Department of Biochemistry and Molecular Biology, University of Salamanca, Spain
Carlos Vicente-Gutiérrez
Institute of Functional Biology and Genomics (IBFG), University of Salamanca, CSIC, Salamanca, Spain; Institute of Biomedical Research of Salamanca (IBSAL), University Hospital of Salamanca, University of Salamanca, CSIC, Salamanca, Spain; CIBERFES, Institute of Health Carlos III, Madrid, Spain
Mauro Corrado
Department of Immunometabolism, Max Planck Institute of Epigenetics and Immunobiology, Freiburg Im Breisgau, Germany
Juan P. Bolaños
Institute of Functional Biology and Genomics (IBFG), University of Salamanca, CSIC, Salamanca, Spain; Institute of Biomedical Research of Salamanca (IBSAL), University Hospital of Salamanca, University of Salamanca, CSIC, Salamanca, Spain; CIBERFES, Institute of Health Carlos III, Madrid, Spain; Department of Biochemistry and Molecular Biology, University of Salamanca, Spain
Luca Scorrano
Veneto Institute of Molecular Medicine, Padova, Italy; Department of Biology, University of Padova, Padova, Italy; Corresponding author. Department of Biology, University of Padova, Padova, Italy.
Reactive oxygen species (ROS) are a common product of active mitochondrial respiration carried in mitochondrial cristae, but whether cristae shape influences ROS levels is unclear. Here we report that the mitochondrial fusion and cristae shape protein Opa1 requires mitochondrial ATP synthase oligomers to reduce ROS accumulation. In cells fueled with galactose to force ATP production by mitochondria, cristae are enlarged, ATP synthase oligomers destabilized, and ROS accumulate. Opa1 prevents both cristae remodeling and ROS generation, without impinging on levels of mitochondrial antioxidant defense enzymes that are unaffected by Opa1 overexpression. Genetic and pharmacologic experiments indicate that Opa1 requires ATP synthase oligomerization and activity to reduce ROS levels upon a blockage of the electron transport chain. Our results indicate that the converging effect of Opa1 and mitochondrial ATP synthase on mitochondrial ultrastructure regulate ROS abundance to sustain cell viability.