Plastoquinone, a very effective electron carrier and
antioxidant of chloroplasts, was conjugated with
decyltriphenylphosphonium to obtain a
cation easily penetrating through membranes. This
cation, called SkQ1, is specifically targeted to mitochondria by electrophoresis in the electric field formed by the mitochondrial respiratory chain. The respiratory chain also regenerates reduced SkQ1H(2) from its oxidized form that appears as a result of the
antioxidant activity of SkQ1H(2). SkQ1H(2) prevents oxidation of
cardiolipin, a mitochondrial
phospholipid that is especially sensitive to attack by
reactive oxygen species (ROS). In cell cultures, SkQ1 and its analog plastoquinonyl decylrhodamine 19 (SkQR1) arrest H(2)O(2)-induced apoptosis. When tested in vivo, SkQs (i) prolong the lifespan of fungi, crustaceans, insects, fish, and mice, (ii) suppress appearance of a large number of traits typical for age-related senescence (
cataract, retinopathies, achromotrichia,
osteoporosis, lordokyphosis, decline of the immune system, myeloid shift of blood cells, activation of apoptosis, induction of β-
galactosidase, phosphorylation of H2AX
histones, etc.) and (iii) lower tissue damage and save the lives of young animals
after treatments resulting in kidney
ischemia,
rhabdomyolysis,
heart attack,
arrhythmia, and
stroke. We suggest that the SkQs reduce mitochondrial ROS and, as a consequence, inhibit mitochondria-mediated apoptosis, an obligatory step of execution of programs responsible for both senescence and fast "biochemical suicide" of an organism after a severe metabolic crisis.