Respiration-dependent uptake and extrusion of Mg2+ by isolated heart mitochondria.

It has been known for some time that isolated heart mitochondria can both take up and extrude Mg2+ by respiration-dependent, uncoupler-sensitive processes. A re-examination of these reactions reveals that the respiration-dependent uptake of Mg2+ can be quite rapid and efficient and is apparently preceded by a passive binding to the inner membrane. The rate of Mg2+ uptake can exceed 30 ng ion/min/mg protein at an efficiency of about 1 ng ion Mg2+ accumulated per ng atom O2 consumed. Passive binding and respiration-dependent accumulation of Mg2+ are strongly inhibited by K+ and other monovalent cations and the uptake reaction is further decreased by the presence of ATP or ADP. Under conditions approaching those faced by mitochondria in situ (state 3 respiration in a KCl medium) the rate of Mg2+ uptake, as estimated from 28Mg2+ distribution, is no more than 0.25 ng ion/min/mg. When heart mitochondria are suspended in a Mg2+-free medium, a slow, respiration-dependent Mg2+ efflux is seen. This reaction is quite insensitive to external K+ and otherwise shows an inhibitor profile markedly different from that of the Mg2+ accumulation reaction. Neither the uptake nor the loss of Mg2+ is inhibited by ruthenium red or diltiazem. These reactions therefore appear unrelated to those involved in the uptake and release of Ca2+. It is concluded that heart mitochondria have separate pathways available for Mg2+ uptake and release.