Detrimental effect of minocycline on mitochondrial function induced by increased permeability to small solutes

Minocyclin (MC) had been considered a neuroprotectant possibly by inhibiting the permeability transition pore of the inner mitochondrial membrane (Zhu, 2002, Nature 417, 74). Doubts on this view, however, were raised when a multicentre, randomised placebo-controlled phase III trial with ALS patients recently showed that MC has harmful effects. This observation has implications for treatment of patients with other neurological disorders as well (Gordon et al., 2007, Lancet Neurol. 6, 1045). In order to cast some light on these contradictory observations we studied the effects of MC on freshly prepared rat liver m…