Role of uncoupled and non-coupled oxidations in maintenance of safely low levels of oxygen and its one-electron reductants

Abstract

To proceed at a high rate, phosphorylating respiration requires ADP to be available. In the resting state, when the energy consumption is low, the ADP concentration decreases so that phosphorylating respiration ceases. This may result in an increase in the intracellular concentrations of O2as well as of one-electron O2reductants such asThese two events should dramatically enhance non-enzymatic formation of reactive oxygen species, i.e. of, and OHׁ, and, hence, the probability of oxidative damage to cellular components. In this paper, a concept is put forward proposing that non-phosphorylating (uncoupled or non-coupled) respiration takes part in maintenance of low levels of both O2and the O2reductants when phosphorylating respiration fails to do this job due to lack of ADP.In particular, it is proposed that some increase in the H+leak of mitochondrial membrane in State 4 lowers, stimulates O2consumption and decreases the level ofwhich otherwise accumulates and serves as one-electron O2reductant. In this connection, the role of natural uncouplers (thyroid hormones), recouplers (male sex hormones and progesterone), non-specific pore in the inner mitochondrial membrane, and apoptosis, as well as of non-coupled electron transfer chains in plants and bacteria will be considered.

Implication of mitochondria-derived reactive oxygen species, cytochrome C and caspase-3 in N-(4-Hydroxyphenyl)retinamide-induced apoptosis in cervical carcinoma cells

“…Recent studies have demonstrated that 4HPR-induced apoptosis in several leukemia and carcinoma cell lines involves ROS induction (Delia et al, 1997;Oridate et al, 1997;Sun et al, 1999). The present investigation addressed the mechanism by which 4HPR induces ROS generation and apoptosis.…”

“…The precise mechanism by which 4HPR increases ROS generation at this site remains to be elucidated and is out of the scope of this investigation. Likewise, additional studies are required to determine whether the 4HPR-induced increase in ROS in leukemia cells (Delia et al, 1997) and head and neck and lung carcinoma cells (Sun et al, 1999) are mediated by mitochondrial CoQ or cyt. B sites.…”

“…Treatment of the C33A cells with CCCP (10 mM), which uncouples electron transfer and ATP synthesis in mitochondria and inhibits the generation of ROS from MRC (Skulachev, 1996), inhibited nearly completely 4HPR-induced ROS generation (Figure 6b). These results demonstrated that MRC is the target of 4HPR e ects on ROS generation.…”

Inhibition of mitochondrial respiratory chain complex I by TNF results in cytochrome c release, membrane permeability transition, and apoptosis

“…Recently, the role of F0F1-ATPase in apoptosis has been suggested (Matsuyama et al, 1998). F0F1-ATPase generates ATP by coupling with the electron transport chain, and this coupling is essential to generate ROS from MRC (Skulachev, 1996). Taken together, MRC complex I inhibition may induce apoptosis through an antioxidant-sensitive pathway by coupling with F0F1-ATPase.…”

“…However, the induction of MPT is not always necessary for the release of cytochrome c (Yang et al, 1997). Several reports have shown that reactive oxygen species (ROS), phospholipases, and Ca 2+ ions can promote the induction of MPT (Skulachev, 1996); however, the link between the stimulus of MPT inducing reagents and the induction of MPT is not clear. Overexpression of bcl-2 abrogated TNF-induced apoptosis, increased mitochondrial membrane potential , and inhibited cytochrome c release (Kluck et al, 1997;Yang et al, 1997).…”