TRPM2 channel in oxidative stress-induced mitochondrial dysfunction and apoptotic cell death.

ABSTRACT

Mitochondria, conserved intracellular organelles best known as the powerhouse of cells for generating ATP, play an important role in apoptosis. Oxidative stress can induce mitochondrial dysfunction and activate mitochondria-mediated apoptotic cell death. TRPM2 is a Ca2+-permeable cation channel that is activated by pathologically relevant concentrations of reactive oxygen species (ROS) and one of its well-recognized roles is to confer susceptibility to ROS-induced cell death. Increasing evidence from recent studies supports TRPM2 channel-mediated cell death as an important cellular mechanism linking miscellaneous oxidative stress-inducing pathological factors to associated diseased conditions. In this chapter, we will discuss the role of the TRPM2 channel in neurons in the brain and pancreatic ß-cells in mediating mitochondrial dysfunction and cell death, focusing mainly on apoptotic cell death, that are induced by pathological stimuli implicated in the pathogenesis of neurodegenerative diseases, ischemic stroke and diabetes.