Journal
BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
Volume 1797, Issue 11, Pages 1775-1779Publisher
ELSEVIER
DOI: 10.1016/j.bbabio.2010.07.002
Keywords
Mitochondria; Permeability Transition; Cyclosporin A; Disease models; Drug screening
Categories
Funding
- Fondazione Cariparo
- University of Padova Progetti di Eccellenza
- Telethon-Italy
- ZF-MODELS IP [LSHG-CT-2003-503496]
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We have studied mitochondrial Ca2+ 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 mitochondria! energy-dependent Ca2+ uptake system that, like the Ca2+ uniporter of mammals, was inhibited by ruthenium red. Zebrafish mitochondria underwent a Ca2+-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]. (C) 2010 Elsevier B.V. All rights reserved.
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