| Mitochondria
functionality. Reduced GSH due to ROS is translocated
into the mitochondria, where it acts as a cofactor for GPx for the
conversion of hydrogen peroxide into water. Due to reduced levels
of GSH, H2O2 keeps on accumulating in the mitochondria,
which diffuses from the mitochondria and starts causing cellular damage.
Adaptor protein p66shc under stress conditions translocates into the
mitochondria and starts producing H2O2 on its
own in the absence of superoxide dismutase, which further leads to
higher levels of H2O2. Stress conditions generated
due to lower mitochondrial glutathione levels cause the oxidation
of the cardiolipin–cytochrome c complex. As a result, cytochrome
c diffuses through the mitochondria via BAX/BAK created pores and
starts the apoptosis via caspase-3. P66shc also reduces the membrane
potential to release cyt c into the cytosol. Upper head arrows show
increased expression, while lower head arrows represent a decreased
expression. Green circles with negative symbol represents membrane
negative potential whereas green circles with plus symbol presents
reduction in the membrane potential. O2•–, superoxide; SOD, superoxide dismutase; H2O2, hydrogen peroxide; GPx, glutathione peroxidase; GSH, glutathione;
GSSG, glutathione disulfide; CLOOH, oxidized cardiolipin; BAX, B-cell
lymphoma-2(Bcl-2)-associated X protein; BAK, Bcl-2 antagonist/killer;
cty c, cytochrome c; p66shc, 66 kDa adaptor protein and member of
the Src homologous-collagen homologue.