Vp. Skulachev, ROLE OF UNCOUPLED AND NON-COUPLED OXIDATIONS IN MAINTENANCE OF SAFELYLOW-LEVELS OF OXYGEN AND ITS ONE-ELECTRON REDUCTANTS, Quarterly Reviews of Biophysics, 29(2), 1996, pp. 169-202
To proceed at a high rate, phosphorylating respiration requires ADP to
be available. In the resting state, when the energy consumption is lo
w, the ADP concentration decreases so that phosphorylating respiration
ceases. This may result in an increase in the intracellular concentra
tions of O-2 as well as of one-electron O-2 reductants such as Q(2)(ra
dical anion). These two events should dramatically enhance non-enzymat
ic formation of reactive oxygen species, i.e. of O-2(radical anion), H
2O, and OH., and, hence, the probability of oxidative damage to cellul
ar 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 O-2 and the O-2 reductants when p
hosphorylating respiration fails to do this job due to lack of ADP. In
particular, it is proposed that some increase in the H+ leak of mitoc
hondrial membrane in State 4 lowers Delta(<(mu)over bar>H+), stimulate
s O-2 consumption and decreases the level of CoQ(radical anion) which
otherwise accumulates and serves as one-electron O-2 reductant. In thi
s connection, the role of natural uncouplers (thyroid hormones), recou
plers (male sex hormones and progesterone), non-specific pore in the i
nner mitochondrial membrane, and apoptosis, as well as of non-coupled
electron transfer chains in plants and bacteria will be considered.