Mitochondrial role in life and death of the cell

Mitochindris are the major ATP producer of the mammalian cell. Moreover, mi tochondria are also the main intracellular source and target of reactive ox ygen species (ROS) that are continually generated as by-products of aerobic metabolism in human cells. A low level of ROS generated from the respirato ry chain was recently proposed to take part in the signaling from mitochond ria to the nucleus. Several structural characteristics of mitochondria and the mitochondrial genome enable them to sense and respond to extracellular and intracellular signals or stresses in order to sustain the life of the c ell,lt has been established that mitochondrial respiratory function decline s with age, and that defects in the respiratory chain increase the producti on of ROS and free radicals in mitochondria, Within a certain concentration range, ROS may induce stress responses of the cell by altering the express ion of a number of genes in order to uphold energy metabolism to rescue the cell. However, beyond this threshold, ROS may elicit apoptosis by inductio n of mitochondrial membrane permeability transition and release of cytochro me c, Intensive research in the past few years has established that mitocho ndria play a pivotal role in the early phase of apoptosis in mammalian cell s. In this article, the role of mitochondria in the determination of life a nd death of the cell is reviewed on the basis of recent findings gathered f rom this and other laboratories. Copyright (C) 2000 National Science Counci l. ROC and S. Karger AG, Basel.