Redox regulation of mitochondrial functional activity by quinones

Abstract

Quinones are among the rare compounds successfully used as therapeutic agents to correct mitochondrial diseases and as specific regulators of mitochondrial function within cells. The aim of the present study was to elucidate the redox-dependent effects of quinones on mitochondrial function. The functional parameters [respiratory activity, membrane potential, and reactive oxygen species (ROS) generation] of isolated rat liver mitochondria and mitochondria in intact cells were measured in the presence of eight exogenously applied quinones that differ in lipophilicity and one-electron reduction potential. The quinones affected the respiratory parameters of mitochondria, and dissipated the mitochondrial membrane potential as well as influenced (either decreased or enhanced) ROS generation, and restored the electron flow during electron transport chain inhibition. The stimulation of ROS production by juglone and 2,5-di-tert-butyl-1,4-benzoquinone was accompanied by a decrease in the acceptor control and respiration control ratios, dissipation of the mitochondrial membrane potential and induction of the reverse electron flow under succinate oxidation in isolated mitochondria. Menadione and 2,3,5-trimethyl-1,4-benzoquinone, which decreased the mitochondrial ROS generation, did not affect the mitochondrial potential and, vice versa, were capable of restoring electron transport during Complex I inhibition. In intact C6 cells, all the quinones, except for coenzyme Q 10 , decreased the mitochondrial membrane potential. Juglone, 1,4-benzoquinone, and menadione showed the most pronounced effects. These findings indicate that quinones with the reduction potential values E 1/2 in the range from −99 to −260 mV were effective redox regulators of mitochondrial electron transport.

Protective effect of 1950 MHz electromagnetic field in human neuroblastoma cells challenged with menadione

“…Conversely, the gene expression of SOD2 (alias, Mn-SOD), the mitochondrial form of superoxide dismutase, was changed by treatments. Literature reports that one of the cytoplasmic organelles most involved in the MD cytotoxic action is the mitochondrion 15,25,26 . In particular, our experiments showed that the pro-oxidant action of MD increased the mRNA level of SOD2, which may reflect higher needs to convert O 2 .− to H 2 O 2 within the mitochondrion 27 .…”

Potential applications of mitochondrial therapy with a focus on Parkinson's disease and mitochondrial transplantation

“…Coenzyme Q: Also called CoQ10, ubiquinone, and ubidecarenone, is found mostly in the interior layer of mitochondria. Ubiquinone, a lipid-soluble benzoquinone with antioxidant activities once reduced to ubiquinol or by CoQ10,promotes rise in vit E. It is placed in the inner membrane of the mitochondria ,is required for electron transfer events in Complex I and II throughout oxidative phosphorylation, and has a significant impact on the formation of ATP 97 . In afflicted areas of preclinical models of PD, seizures, and ischemia, CoQ10 protects to neuronal cells from oxidative stress CoQ10 has been extensively studied as a treatment for neurological illnesses, both in preclinical studies and clinical trials, investigations due to its multiple mitochondrial therapeutic properties and severe mitochondrial dysfunction 98 .…”

Fabrication of plumbagin on silver nanoframework for tunable redox modulation: Implications for therapeutic angiogenesis

“…Decades ago, various natural sources and drugs were identified to modulate angiogenesis. The Quinone compounds with the reduction potential values E 1/2 in the range from −99 to −260 mV were found to be effective redox regulators of mitochondrialelectron-transport-induced oxidative stress in biological systems (Krylova et al, 2016). Recently, plumbagin has been identified as a potent antitumorigenic molecule due to its redox modulating effect (Lai et al, 2012).…”