Aspects of human bioenergetics as studied in vivo by magnetic resonance spectroscopy.

Author

Barbiroli B, Iotti S, Lodi R

Date

10/1998

Journal

Biochimie

Abstract

We outline the relevant capabilities of in vivo phosphorus MR spectroscopy by discussing some aspects of normal human biochemistry as studied by this technique. The transport of inorganic phosphate from cytosol into mitochondria in the human skeletal muscle was studied by exploiting a new experimental protocol. We found that Pi was transported into mitochondria in the absence of ATP biosynthesis and in the presence of a pH gradient. The control of CoQ on the efficiency of oxidative phosphorylation in the skeletal muscle and brain was studied by administering CoQ to patients with mitochondrial cytopathies due to known enzyme defects. Before CoQ we had detected a relevant reduction of mitochondrial functionality in the skeletal muscle as shown by the reduced rate of phosphocreatine recovery from exercise, and in the occipital lobes by reduced [phosphocreatine] and a high [ADP] and [Pi]. After CoQ all brain variables were remarkably improved. Treatment with CoQ also improved the rate of muscle phosphocreatine recovery from exercise. Our in vivo findings support the hypothesis that the concentration of CoQ rather than the rate of its lateral diffusion in the mitochondrial membrane controls the efficiency of oxidative phosphorylation. Other experiments were undertaken to clarify the functional relationship between cytosolic free [Mg2+] and cell bioenergetics in the intact human brain. In the same group of patients with mitochondrial cytopathies we found decreased delta G of ATP hydrolysis and low cytosolic free [Mg2+]. Treatment with CoQ resulted in improved brain bioenergetics and increased free [Mg2+]. These findings strongly indicate that decreased free magnesium was secondary to defective mitochondrial respiration, and support the hypothesis that cytosolic free [Mg2+] is regulated in the intact brain cell to equilibrate, at least in part, any changes in rapidly available free energy.