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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Tissue and sex specificities in Ca2+ handling by isolated mitochondria in conditions avoiding the permeability transition

Texto completo
Autor(es):
Chweih, Hanan [1] ; Castilho, Roger F. [1] ; Figueira, Tiago R. [1]
Número total de Autores: 3
Afiliação do(s) autor(es):
[1] Univ Estadual Campinas, Dept Clin Pathol, Fac Med Sci, Campinas, SP - Brazil
Número total de Afiliações: 1
Tipo de documento: Artigo Científico
Fonte: Experimental Physiology; v. 100, n. 9, p. 1073-1092, SEP 1 2015.
Citações Web of Science: 14
Resumo

New Findings What is the central question of this study? The assessment of Ca2+ handling by isolated mitochondria can be biased by dysfunctions secondary to Ca2+-induced mitochondrial permeability transition (MPT). As a result of this uncertainty and the differing experimental conditions between studies, the tissue and sex diversities in mitochondrial Ca2+ transport are still unsettled questions. What is the main finding and its importance? If MPT is not prevented during Ca2+ transport assays, some measured variables are biased. Accounting for the implied importance of preventing MPT, we observed substantial tissue specificities in the mitochondrial Ca2+ handling, particularly in the Ca2+ efflux pathways. The characteristics of mitochondria, including their Ca2+ transport functions, may exhibit tissue specificity and sexual dimorphism. Given that measurements of Ca2+ handling by isolated mitochondria may be biased by dysfunction secondary to Ca2+-induced mitochondrial permeability transition (MPT) pore opening, this study evaluated the extent to which MPT inhibition by ciclosporin affected the measurement of Ca2+ transport in isolated rat liver mitochondria. The results indicate that the steady-state levels of external Ca2+ and the rates of mitochondrial Ca2+ efflux through the selective pathways can be overestimated by up to fourfold if MPT pore opening is not prevented. We analysed Ca2+ transport in isolated mitochondria from the liver, skeletal muscle, heart and brain of male and female rats in incubation conditions containing MPT inhibitors, NAD-linked substrates and relevant levels of free Ca2+, Mg2+ and Na+. The Ca2+ influx rates were similar among the samples, except that the liver mitochondria displayed values fourfold higher. In contrast, the Ca2+ efflux rates exhibited more tissue diversity, especially in the presence of Na+. Interestingly, the Na+-independent Ca2+ efflux was highest in the heart mitochondria (approximate to 4nmolmg(-1)min(-1)), thus challenging the view that cardiac mitochondrial Ca2+ efflux relies almost exclusively on a Na+-dependent pathway. Sex specificity was observed in only two kinetic indexes of heart mitochondrial Ca2+ homeostasis and in the ADP-stimulated respiration of liver mitochondria (approximate to 20% higher in females). The present study shows the methodological importance of preventing MPT when measuring the properties and the physiological variability of the Ca2+ handling by isolated mitochondria. (AU)

Processo FAPESP: 11/51800-1 - Dano muscular induzido por exercício excêntrico: envolvimento da mitocôndria e interações com a miotoxicidade da estatina
Beneficiário:Tiago Rezende Figueira
Linha de fomento: Bolsas no Brasil - Pós-Doutorado
Processo FAPESP: 11/50400-0 - Metabolismo energético, estado redox e funcionalidade mitocondrial na morte celular e em desordens cardiometabólicas e neurodegenerativas
Beneficiário:Aníbal Eugênio Vercesi
Linha de fomento: Auxílio à Pesquisa - Temático