Mitochondrial Ca²⁺ and Reactive Oxygen Species in Trypanosomatids

Millions of people are infected with trypanosomatids and new therapeutic approaches are needed. Trypanosomatids possess one mitochondrion per cell and its study has led to discoveries of general biological interest. These mitochondria, as in their animal counterparts, generate reactive oxygen species (ROS) and have evolved enzymatic and nonenzymatic defenses against them. Mitochondrial calcium ion (Ca²⁺) overload leads to generation of ROS and its study could lead to relevant information on the biology of trypanosomatids and to novel drug targets. Mitochondrial Ca²⁺ is normally involved in maintaining the bioenergetics of trypanosomes, but when Ca²⁺ overload occurs, it is associated with cell death. Trypanosomes lack key players in the mechanism of cell death described in mammalian cells, although mitochondrial Ca²⁺ overload results in collapse of their membrane potential, production of ROS, and cytochrome c release. They are also very resistant to mitochondrial permeability transition, and cell death after mitochondrial Ca²⁺ overload depends on generation of ROS. In this review, we consider the mechanisms of mitochondrial oxidant generation and removal and the involvement of Ca²⁺ in trypanosome cell death. More studies are required to determine the reactions involved in generation of ROS by the mitochondria of trypanosomatids, their enzymatic and nonenzymatic defenses against ROS, and the occurrence and composition of a mitochondrial permeability transition pore. Antioxid. Redox Signal. 36, 969-983.