title: OPA1 promotes pH flashes that spread between contiguous mitochondria without matrix protein exchange.
abstract: The chemical nature and functional significance of mitochondrial flashes associated with fluctuations in mitochondrial membrane potential is unclear. Using a ratiometric pH probe insensitive to superoxide, we show that flashes reflect matrix alkalinization transients of ∼0.4 pH units that persist in cells permeabilized in ion-free solutions and can be evoked by imposed mitochondrial depolarization. Ablation of the pro-fusion protein Optic atrophy 1 specifically abrogated pH flashes and reduced the propagation of matrix photoactivated GFP (paGFP). Ablation or invalidation of the pro-fission Dynamin-related protein 1 greatly enhanced flash propagation between contiguous mitochondria but marginally increased paGFP matrix diffusion, indicating that flashes propagate without matrix content exchange. The pH flashes were associated with synchronous depolarization and hyperpolarization events that promoted the membrane potential equilibration of juxtaposed mitochondria. We propose that flashes are energy conservation events triggered by the opening of a fusion pore between two contiguous mitochondria of different membrane potentials, propagating without matrix fusion to equilibrate the energetic state of connected mitochondria.
authors.affiliation: Department of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland.
authors.forename: Jaime
authors.initials: J
authors.lastname: Santo-Domingo
authors.forename: Marta
authors.initials: M
authors.lastname: Giacomello
authors.forename: Damon
authors.initials: D
authors.lastname: Poburko
authors.forename: Luca
authors.identifier: 0000000285158928
authors.initials: L
authors.lastname: Scorrano
authors.forename: Nicolas
authors.identifier: 0000000299336772
authors.initials: N
authors.lastname: Demaurex
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D034281:Dynamins / Q000502:physiology*; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D004734:Energy Metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008164:Luminescent Proteins / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D008164:Luminescent Proteins; C054562:yellow fluorescent protein, Bacteria; D013481:Superoxides; D049452:Green Fluorescent Proteins; D020558:GTP Phosphohydrolases; C415198:OPA1 protein, human; C498809:Opa1 protein, mouse; C486391:Dnm1l protein, mouse; D034281:Dynamins; D002118:Calcium