Opa1 relies on cristae preservation and ATP synthase to curtail reactive oxygen species accumulation in mitochondria
Year: 2021
Type: article
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.
Source: Redox Biology
Institutions: Consejo Superior de Investigaciones Científicas, Universidad de Salamanca, Instituto de Salud Carlos III, Instituto de Investigación Biomédica de Salamanca, Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable, Instituto de Biología Funcional y Genómica, Max Planck Institute of Immunobiology and Epigenetics, University of Padua, Veneto Institute of Molecular Medicine
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,450
Funders: Muscular Dystrophy Association, Fundación BBVA, Fondazione Cassa di Risparmio di Padova e Rovigo, Fundación Ramón Areces, FP7 Coherent Development of Research Policies, Fondation Leducq, Ministero dell’Istruzione, dell’Università e della Ricerca, Università degli Studi di Padova, Fondazione Umberto Veronesi, Associazione Italiana per la Ricerca sul Cancro, Banco Bilbao Vizcaya Argentaria, Servier, Horizon 2020 Framework Programme, Instituto de Salud Carlos III, Agencia Estatal de Investigación
Awards: G1171198284, G1175115578, G176523928, G2262748287, MDA Research Grant, Winter 2019 (Mitochondrial Myopathy: Luca Scorrano), G2643629490, G300979063, G3480869486, Exploring the role of mitochondrial dynamics in cancer signaling cascades: integrating HIF1, hedgehog and Rap1, G41939404, G425668148, G4347308769, G4449632905, G5080475149, G5175525644, G6315092050, G683931746, G7169023097, G782883926, G8167330452, G8520508164, G867133708, G8684520763, G8824911526
OpenAlex ID: W3136393485