Regulation of ATP Synthesis in Mitochondria

Abstract

Regulation of ATP synthesis in mitochondria has been an early example for recognizing regulatory problems in a sequence of metabolic reactions. Still 20 years later it attracts intense attention and is presently again in the focus of new formalism on systems control. Early, respiratory control was mainly regarded as dependent on the concentration of ADP [1, 2]. However, a few years later in context with the reversibility of electron transport, we observed that the control is also dependent on the ATP concentration, such that more the ratio of ATP/ADP seemed to be the controlling entity [3, 4]. At that state, it was not yet known that oxidative phosphorylation in mitochondria is masked by a transport system which exports the ATP synthesized inside the mitochondria against the uptake of ADP. The discovery of this exchange system [5] changed drastically the scene for analyzing the control of ATP synthesis in mitochondria. In fact, control of ATP production by mitochondria is fairly well-understood on the level of transport, but not yet on the level of synthesis per se.