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Opa1 relies on cristae preservation and ATP synthase to curtail reactive oxygen species accumulation in mitochondria
- Source :
- Redox Biology : an official journal of the Society for Free Radical Biology and Medicine, Redox Biology, Vol 41, Iss, Pp 101944-(2021), Digital.CSIC. Repositorio Institucional del CSIC, instname, Redox Biology
- Publication Year :
- 2021
-
Abstract
- 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.<br />Graphical abstract Image 1<br />Highlights • Mitochondrial ROS levels mirror changes in cristae shape. • F1FO-ATP synthase oligomerization and reversal link mitochondrial ultrastructure to ROS generation. • Disrupted F1FO-ATP synthase dimerization abolishes Opa1 ability to curtail mitochondrial ROS accumulation.
- Subjects :
- 0301 basic medicine
Medicine (General)
endocrine system
Bioenergetics
QH301-705.5
Clinical Biochemistry
Mitochondrion
Biochemistry
Opa1
GTP Phosphohydrolases
Mitochondrial Proteins
ATP synthase
03 medical and health sciences
Adenosine Triphosphate
0302 clinical medicine
R5-920
Viability assay
Biology (General)
F1FO-ATP synthase [Opa1]
Mitochondrial cristae
chemistry.chemical_classification
Reactive oxygen species
biology
F1FO-ATP synthase
Organic Chemistry
ROS
Opa1: F1FO-ATP synthase
Electron transport chain
eye diseases
Mitochondria
Cell biology
030104 developmental biology
Enzyme
F
1
O
Ultrastructure
mitochondrial fusion
chemistry
Mitochondrial Membranes
biology.protein
Reactive Oxygen Species
030217 neurology & neurosurgery
Research Paper
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Redox Biology : an official journal of the Society for Free Radical Biology and Medicine, Redox Biology, Vol 41, Iss, Pp 101944-(2021), Digital.CSIC. Repositorio Institucional del CSIC, instname, Redox Biology
- Accession number :
- edsair.doi.dedup.....161586bad8cfc8eb4b5a0fc9274253ff