Mitochondria: a hub of redox activities and cellular distress control

Abstract

In their reductionist approach in unraveling phenomena inside the cell, scientists in recent times have focused attention to mitochondria. An organelle with peculiar evolutionary history and organization, it is turning out to be an important cell survival switch. Besides controlling bioenergetics of a cell it also has its own genetic machinery which codes 37 genes. It is a major source of generation of reactive oxygen species, acts as a safety device against toxic increases of cytosolic Ca2+ and its membrane permeability transition is a critical control point in cell death. Redox status of mitochondria is important in combating oxidative stress and maintaining membrane permeability. Importance of mitochondria in deciding the response of cell to multiplicity of physiological and genetic stresses, inter-organelle communication, and ultimate cell survival is constantly being unraveled and discussed in this review. Mitochondrial events involved in apoptosis and necrotic cell death, such as activation of Bcl-2 family proteins, formation of permeability transition pore, release of cytochrome c and apoptosis inducing factors, activation of caspase cascade, and ultimate cell death is the focus of attention not only for cell biologists, but also for toxicologists in unraveling stress responses. Mutations caused by ROS to mitochondrial DNA, its inability to repair it completely and creation of a vicious cycle of mutations along with role of Bcl-2 family genes and proteins has been implicated in many diseases where mitochondrial dysfunctions play a key role. New therapeutic approaches toward targeting low molecular weight compounds to mitochondria, including antioxidants is a step toward nipping the stress in the bud.