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

Redox Biol. 2021 May:41:101944. doi: 10.1016/j.redox.2021.101944. Epub 2021 Mar 19.

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.

Keywords: Bioenergetics; F(1)F(O)-ATP synthase; Mitochondrial cristae; Opa1; ROS; Ultrastructure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • GTP Phosphohydrolases* / metabolism
  • Mitochondria
  • Mitochondrial Membranes* / metabolism
  • Mitochondrial Proteins / metabolism
  • Reactive Oxygen Species / metabolism

Substances

  • Mitochondrial Proteins
  • Reactive Oxygen Species
  • Adenosine Triphosphate
  • GTP Phosphohydrolases