Artículo del mes
febrero 2022

Opa1 relies on cristae preservation and ATP synthase to curtail reactive oxygen species accumulation in mitochondria

Referencia artículo:
Redox Biology Volume 41, May 2021, 10194.7
Las crestas mitocondriales son las plataformas lipídicas en las que se estabilizan los (super)complejos respiratorios. Aquí demostramos que la estructura de estas crestas responde a condicionantes metabólicos para determinar los niveles de especies reactivas de oxígeno (ROS). Para ello, la proteína de andamiaje de crestas Opa1 favorece la estabilización de oligómeros de F1FO-ATP sintasa y su actividad reversa tras inhibición de la respiración mitocondrial, reduciendo ROS y promoviendo la supervivencia celular.
Resumen
Reactive oxygen species (ROS) area 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.
Sobre el grupo investigador