title: Increased Susceptibility of Gracilinanus microtarsus Liver Mitochondria to Ca²⁺-Induced Permeability Transition Is Associated with a More Oxidized State of NAD(P).
abstract: In addition to be the cell's powerhouse, mitochondria also contain a cell death machinery that includes highly regulated processes such as the membrane permeability transition pore (PTP) and reactive oxygen species (ROS) production. In this context, the results presented here provide evidence that liver mitochondria isolated from Gracilinanus microtarsus, a small and short life span (one year) marsupial, when compared to mice, are much more susceptible to PTP opening in association with a poor NADPH dependent antioxidant capacity. Liver mitochondria isolated from the marsupial are well coupled and take up Ca(2+) but exhibited a much lower Ca(2+) retention capacity than mouse mitochondria. Although the known PTP inhibitors cyclosporin A, ADP, and ATP significantly increased the marsupial mitochondria capacity to retain Ca(2+), their effects were much larger in mice than in marsupial mitochondria. Both fluorescence and HPLC analysis of mitochondrial nicotinamide nucleotides showed that both content and state of reduction (mainly of NADPH) were lower in the marsupial mitochondria than in mice mitochondria despite the similarity in the activity of the glutathione peroxidase/reductase system. Overall, these data suggest that PTP opening is an important event in processes of Ca(2+) signalling to cell death mediated by mitochondrial redox imbalance in G. microtarsus.
authors.affiliation: Department of Clinical Pathology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), 13087-877 Campinas, SP, Brazil.
authors.forename: Juliana A
authors.initials: JA
authors.lastname: Ronchi
authors.affiliation: Graduate Program in Ecology, Biology Institute, State University of Campinas, 13087-877 Campinas, SP, Brazil.
authors.forename: Barbara
authors.initials: B
authors.lastname: Henning
authors.affiliation: Department of Clinical Pathology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), 13087-877 Campinas, SP, Brazil.
authors.forename: Felipe G
authors.initials: FG
authors.lastname: Ravagnani
authors.affiliation: Department of Clinical Pathology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), 13087-877 Campinas, SP, Brazil.
authors.forename: Tiago R
authors.initials: TR
authors.lastname: Figueira
authors.affiliation: Department of Clinical Pathology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), 13087-877 Campinas, SP, Brazil.
authors.forename: Roger F
authors.initials: RF
authors.lastname: Castilho
authors.affiliation: Department of Animal Biology, Biology Institute, State University of Campinas, 13087-877 Campinas, SP, Brazil.
authors.forename: Sergio F
authors.initials: SF
authors.lastname: dos Reis
authors.affiliation: Department of Clinical Pathology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), 13087-877 Campinas, SP, Brazil.
authors.forename: Anibal E
authors.initials: AE
authors.lastname: Vercesi
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D016572:Cyclosporine / Q000494:pharmacology; D005979:Glutathione Peroxidase / Q000378:metabolism; D007477:Ions / Q000737:chemistry; D008136:Longevity; D008394:Marsupialia / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D008930:Mitochondria, Liver / Q000201:enzymology / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000083162:Mitochondrial Permeability Transition Pore; D009243:NAD / Q000032:analysis / Q000737:chemistry*; D009250:NADP Transhydrogenases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D007477:Ions; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D017382:Reactive Oxygen Species; D009243:NAD; D000244:Adenosine Diphosphate; D016572:Cyclosporine; D000255:Adenosine Triphosphate; D005979:Glutathione Peroxidase; D009250:NADP Transhydrogenases; D002118:Calcium