Figure 2.

General links in mitochondria-dependent pathways of intracellular apoptosis induction by different-valence heavy metals. Heavy metals (Ag⁺, Tl⁺, Hg²⁺, Cd²⁺, Pb²⁺, As³⁺, Sb³⁺, Al³⁺, Ga³⁺, In³⁺, Cr⁶⁺, and U⁶⁺) induce mitochondrial permeability transition pore (MPTP) opening, which is accompanied by cytochrome c release into the intermembrane space. As a result of this process, caspases-3 and -9 are activated and trigger apoptosis induction. Some metals (Cd²⁺, As³⁺, Al³⁺, and In³⁺) damage DNA, resulting in bax and p53 activation that induces apoptotic processes. Arrows show MPTP induction. Bold vertical arrows show the sequence of events associated with mitochondria during the induction of intracellular apoptosis by heavy metals. Apoptosis induction pathways associated with DNA damage are indicated by horizontal arrows. Abbreviations: Cyt. C, cytochrome C; MPTP, mitochondrial permeability transition pore.