Substrate-dependent effect of phenolic antioxidants on Ca²⁺accumulation by rat liver mitochondria

Abstract

The effect of different phenolic antioxidants on mitochondrial Ca2+ capacity (maximum amount of Ca2+ mitochondria can accumulate) was studied. Butylated hydroxytoluene substantially enhanced the Ca2+ capacity in mitochondria oxidizing succinate, butylated hydroxyanisole had a moderate effect while 2,5-di-(t-butyl)- 1,4 benzohydroquinone did not affect Ca2+ capacity at all. The analysis of Ca2+ accumulation in mitochondria oxidizing succinate in the presence of 2,5-di-(t-butyl)-1,4 benzohydroquinone revealed inhibition of the rate of Ca2+ accumulation. This effect was absent when ATP hydrolysis or NAD+-dependent substrate oxidation supported Ca2+ transport. Direct measurements of oxygen consumption revealed the concentration-dependent inhibition of succinate oxidation by increasing concentrations of 2,5-di-(t-butyl)- 1,4 benzohydroquinone. When succinate was substituted by NAD+-dependent respiratory substrates, the Ca2+ capacity of mitochondria with 2,5-di-(t-butyl)-1,4 benzohydroquinone was even higher than in the presence of butylated hydroxytoluene.

Gene expression profiling for human iPS-derived motor neurons from sporadic ALS patients reveals a strong association between mitochondrial functions and neurodegeneration

“…Because mitochondria regulate intracellular iron homeostasis (Horowitz and Greenamyre, 2010 ), HFE deregulation may represent an additional mitochondrial-based pathogenic mechanism in sporadic ALS. Mitochondrial dysfunction leading to cell autonomous neuronal damage in sporadic ALS is also supported by the significant deregulation of both TOMM20L (Ryan and Gogvadze, 1999 ) and HtrA2/Omi (Srinivasula et al, 2003 ), as seen in our microarray analysis.…”