Physiological cyanide concentrations do not stimulate mitochondrial cytochrome

Randi et al. (1) claim that vanishingly small concentrations of cyanide added to human cell lines 1) increases cell proliferation, 2) reduces the basal glutathionylation of bovine cytochrome c oxidase (CcO), 3) increases the steady-state activity of CcO, and 4) produces spectral changes of purified CcO. Our criticism arises from the following. First, we have reproduced the effect of 1 nM cyanide on the respiration of mouse liver mitochondria by using the tetramethyl- p -phenylene diamine (TMPD)–ascorbate reducing system and found no evidence for increased CcO activity (Fig. 1 A ). Fig. 1. ( A ) Effect of 1 nM and 100 μM cyanide (CN) on the respiration of rotenone- and antimycin-treated mouse liver mitochondria by using the TMPD–ascorbate system. Briefly, 20 mg of purified mitochondria were incubated with 1 nM or 100 μM KCN for 15 min in resuspension buffer (75 mM sucrose, Hepes 20 mM, 50 mM KCl, 1 mM NaH2PO4, 1 mM MgCl2, and 1 mM EGTA, pH 7.4). The respiratory activity of mouse liver mitochondria was measured with a Clark-type electrode, in an all-glass reaction chamber magnetically stirred, at 25 °C. … [↵][1]1To whom correspondence may be addressed. Email: francesco.malatesta{at}uniroma1.it. [1]: #xref-corresp-1-1