This report summarizes recent work in our laboratory aimed at understanding protein-mediated mitochondrial cation transport. We are studying three distinct cation cycles that contain porters catalyzing influx and efflux of cations between cytosol and mitochondrial matrix. Each of these cation cycles plays a major physiological role in the overall energy economy. The K+ cycle maintains the integrity of the vesicular structure and includes the K+/H+ antiporter, the KATP channel, and K+ leak driven by the high membrane potential. The Ca2+ cycle relays the signals calling for modulation of ATP production and includes the Ca2+ channel, the Na+/Ca2+ antiporter, and the Na+/H+ antiporter. The H+ cycle of brown adipose tissue mitochondria provides heat to hibernating and newborn mammals and consists of the uncoupling protein, which catalyzes regulated H+ influx.