Low brain intracellular free magnesium in mitochondrial cytopathies

The authors studied, by in vivo phosphorus magnetic resonance spectroscopy (P-31-MRS), the occipital lobes of 19 patients with mitochondrial cytopathi es to clarify the functional relation between energy metabolism and concent ration of cytosolic free magnesium. All patients displayed defective mitoch ondrial respiration with low phosphocreatine concentration [PCr] and high i norganic phosphate concentration [Pi] and [ADP]. Cytosolic free [Mg2+] and the readily available free energy (defined as the actual free energy releas ed by the exoergonic reaction of ATP hydrolysis, i.e., Delta G(ATPhyd)) wer e abnormally low in all patients. Nine patients were treated with coenzyme Q(10) (CoQ), which improved the efficiency of the respiratory chain, as sho wn by an increased [PCr], decreased [Pi] and [ADP], and increased availabil ity of free energy (more negative value of Delta G(ATPhyd)). Treatment with CoQ also increased cytosolic free [Mg2+] in all treated patients. The auth ors findings demonstrate low brain free [Mg2+] in our patients and indicate that it resulted from failure of the respiratory chain. Free Mg2+ contribu tes to the absolute value of Delta G(ATPhyd). The results also are consiste nt with the view that cytosolic [Mg2+] is regulated in the intact brain cel l to equilibrate, at least in part, any changes in rapidly available free e nergy.