NADH-linked substrate-mediated enhancement of mitochondrial calcium accumulation and DNA single-strand breakage elicited by tert- butylhydroperoxide: The source of the cation is a ryanodine-sensitive calcium store

Andrea Guidarelli, Emilio Clementi, Liliana Brambilla, Orazio Cantoni

Research output: Contribution to journalArticle


We previously found that the membrane-permeant NADH-linked substrates pyruvate and β-hydroxybutyrate enhance the formation of DNA single-strand breaks induced by tert-butylhydroperoxide (tB-OOH) in intact U937 cells. This effect is mediated by a process involving enforced mitochondrial calcium accumulation in the absence of discernible elevation in the cytosolic concentration of free calcium ions. We now show that the intracellular source of the cation is a ryanodine-sensitive calcium store. A high concentration of ryanodine, which suppressed the caffeine-mediated mobilization of calcium ions, also abolished the effects of the NADH-linked substrates on the mitochondrial accumulation of the cation as well as on the tB-OOH-induced genotoxic response. These data constitute a novel demonstration of a physiological mechanism with important pathological implications.

Original languageEnglish
Pages (from-to)65-69
Number of pages5
JournalExperimental Cell Research
Issue number1
Publication statusPublished - May 25 1999


ASJC Scopus subject areas

  • Cell Biology

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