The Role of Mitochondria in the Control of Cellular Calcium Homeostasis

Abstract

Demonstration of an active Ca²⁺ transport system in the mitochondrial inner membrane has led to investigation of the physiological function of this activity. Control of intracellular Ca²⁺ ion homeostasis and/or modulation of mitochondrial metabolism may be important consequences of Ca²⁺ flux across the mitochondrial membrane. Distribution of Ca²⁺ between the cytosol and the two major intracellular Ca²⁺ transport organelles (the mitochondria and the reticular network) will be determined by the environmental levels of Ca²⁺ and the kinetic constants of each system. The high affinity (but low capacity) of the reticulum for Ca²⁺ is within the range of cytosolic Ca²⁺ buffering, i.e., from 150–200 nM, and is dealt with elsewhere in this symposium. The ability of the mitochondria to respond to changing Ca²⁺ concentrations in order to activate metabolism or to buffer cytosolic Ca²⁺ is dependent upon intracellular conditions which may affect the transporters. Mitochondrial Ca²⁺ flux Is controlled by both an import pathway and an export pathway which are thought to operate in parallel. Any alteration in the balance between the two pathways can affect cytosolic Ca²⁺ buffering and/or modulate energy production via Ca²⁺ sensitive dehydrogenase activities in the mitochondrial matrix. Mitochondrial Ca²⁺ uptake is a low affinity, high capacity process, linked to the fundamental energy producing mechanism across the inner membrane.