MITOCHONDRIAL CALCIUM-UPTAKE FROM PHYSIOLOGICAL-TYPE PULSES OF CALCIUM - A DESCRIPTION OF THE RAPID UPTAKE MODE

A controversy in the field of bioenergetics has been whether mitochond ria are capable of sequestering enough Ca2+ from cytosolic Ca2+ pulses to raise their intramitochondrial free Ca2+ level ([Ca2+](m)). This i s significant because an increase in [Ca2+](m) has been linked to an i ncrease in cellular metabolic rate through various mechanisms, To reso lve this question, we exposed isolated liver mitochondria to physiolog ical type pulses of Ca2+ produced using a pulse-generating system (Spa ragna, G. C., Gunter, K. K., and Gunter, T. E. (1994) Anal. Biochem. 2 19, 96-103). We then measured the resulting mitochondrial Ca2+ uptake, The uniporter was previously thought to be the only specific Ca2+ upt ake mechanism in mitochondria, Our studies have uncovered an additiona l uptake mechanism, the rapid mode of uptake or RaM, which functions a t the beginning of each pulse and allows mitochondria to sequester a c onsiderable amount of Ca2+ from short pulses, We have shown that the R aM is reset by decreasing the [Ca2+] between pulses for a very short t ime, making this uptake mode ideally suited for Ca2+ sequestration fro m Ca2+ pulse sequences, With rapid Ca2+ uptake occurring at the beginn ing of each pulse, liver mitochondria may be able to sequester suffici ent Ca2+ from a short sequence of pulses to activate the cellular meta bolic rate.