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.
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.
Redox Biol. 2021 May;41:101944. doi: 10.1016/j.redox.2021.101944. Epub 2021 Mar 19.
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.
活性氧（ROS）是线粒体嵴中活跃的线粒体呼吸产生的常见产物，但嵴的形状是否会影响 ROS 水平尚不清楚。在这里，我们报告说线粒体融合和嵴形状蛋白 Opa1 需要线粒体 ATP 合酶寡聚体来减少 ROS 的积累。在以半乳糖为燃料的细胞中，通过线粒体强制产生 ATP，嵴增大，ATP 合酶寡聚体不稳定，ROS 积累。Opa1 可防止嵴重塑和 ROS 的产生，而不会影响线粒体抗氧化防御酶的水平，而过表达 Opa1 不会影响这些酶的水平。遗传和药理学实验表明，在电子传递链受阻时，Opa1 需要 ATP 合酶寡聚化和活性来降低 ROS 水平。我们的结果表明，Opa1 和线粒体 ATP 合酶对线粒体超微结构的汇聚作用调节 ROS 的丰度以维持细胞活力。
