Regulation of Respiration by Cellular Key Parameters: Energy Demand, ADP, and Mg 2+

In non-photosynthetic tissues most of cell’s demand for ATP is met by mitochondrial oxidative phosphorylation. Surprisingly, however, although the mechanisms involved in ATP synthesis are now well known, our understanding the regulation of cell respiration is still incomplete. Nevertheless, recent results suggest that free ADP concentration plays a critical role in adjusting the rate of respiratory ATP synthesis. Quite generally, respiration is not a limiting factor for Mg-ATP regeneration, because under diverse physiological situations (except after blocking or uncoupling the respiratory electron chain, or during Mg-starvation) no significant accumulation of ADP is observed. Based on in vivo31P-NMR experiments in sycamore cells, recent results summarized in this chapter show that the cytosolic concentrations of free ADP and free Mg2+, rather than the ATP/ADP ratio (or the energy charge), are the key factors adjusting cellular respiratory activity to the metabolic Mg-ATP demand. In most physiological situations, cytosolic free ADP concentration is low (20 μM) and stable, unlike that of ATP. Because this value is close to the reported Km(ADP) of the mitochondrial ADP/ATP carrier, it seems likely that this carrier regulates cytosolic free ADP concentration. Under standard conditions, the moderate cytosolic Mg2+ concentration (250 μM) and the high matricial Mg2+ concentration (2.4 mM) allow ADP/ATP exchange across the mitochondrial inner membrane. In addition, cytosolic Mg2+ concentration is remarkably stable suggesting that the response of respiration to Mg-ATP requirement is effectively mediated by cytosolic free ADP rather than Mg2+ concentration itself.