Mitochondrial Ca2+ transport and permeability transition in zebrafish (Danio rerio).
We have studied mitochondrial Ca(2+) transport and the permeability transition (PT) in the teleost zebrafish (Danio rerio), a key model system for human diseases. Permeabilized zebrafish embryo cells displayed a mitochondrial energy-dependent Ca(2+) uptake system that, like the Ca(2+) uniporter of mammals, was inhibited by ruthenium red. Zebrafish mitochondria underwent a Ca(2+)-dependent PT that displayed Pi-dependent desensitization by cyclosporin A, and responded appropriately to key modulators of the mammalian PT pore (voltage, pH, ubiquinone 0, dithiol oxidants and cross linkers, ligands of the adenine nucleotide translocator, arachidonic acid). Opening of the pore was documented in intact cells, where it led to death that could largely be prevented by cyclosporin A. Our results represent a necessary step toward the use of zebrafish for the screening and validation of PTP inhibitors of potential use in human diseases, as recently shown for collagen VI muscular dystrophy [Telfer et al., 2010].
Azzolin
Luca
L
Department of Biomedical Sciences and CNR Institute of Neuroscience, University of Padua, Italy.
Basso
Emy
E
Argenton
Francesco
F
Bernardi
Paolo
P
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002463:Cell Membrane Permeability / Q000502:physiology*; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000502:physiology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000187:drug effects / Q000378:metabolism*; D000083162:Mitochondrial Permeability Transition Pore; D015027:Zebrafish
D002121:Calcium Channel Blockers; D007166:Immunosuppressive Agents; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D016572:Cyclosporine; D002118:Calcium