Apoptosis, a specific type of programmed cell death, is characterized by cell shrinkage, nucleus
condensation and fragmentation, plasma membrane blebbing and final engulfment by neighboring cells or
professional phagocytes. The molecular mechanisms of organotin-induced apoptosis, which involve a series of
biochemical regulators and molecular interactions, have been extensively studied in different cell types but the
apoptotic pathway mechanisms and signaling still remain unexplained in some detail. Apoptosis may be triggered
and modulated by caspase-independent, and more frequently by caspase-dependent pathways. Pro-caspase
activation is driven by death receptors, and/or by a mitochondrion-mediated mechanism. Although both pathways
were described, the mitochondrial mechanism seems to be the most important one in organotin-induced
apoptosis. Organotin compounds trigger cytoskeletal modifications and disruption of mitochondrial functions.
Generally, the apoptotic pathway induced by organotins starts with their interactions with cellular components
leading to perturbation of intracellular Ca2+ homeostasis, the latter especially triggered by endoplasmic reticulum
stress, and intracellular Ca2+ concentration increase, cessation of ATP and reactive oxygen species production and
loss of mitochondrial membrane potential. These events are followed by cytochrome c release from mitochondria
to cytosol, apoptosome formation and final executioner caspase activation. The increase in intracellular Ca2+ level
and the consequent mitochondrial cytochrome c release play critical steps in organotin-induced apoptosis. The
process not only depends on cell type and sensitivity but also on organotin chemical characteristics and insult
intensity. New and promising research on mechanisms of organotin-induced apoptosis is focused on the
characterization of organotin interactions with apoptosis-related proteins and regulation of gene expression.
Keywords: Apoptosis - organotin-caspase modulation - endoplasmic reticulum stress - intracellular (Ca2+)-
oxidative stress - mitochondria - MAP-kinase.
