Cellular energy in the form of ATP can be produced
through oxidative phosphorylation and through
glycolysis. Since oxidative phosphorylation requires
oxygen and generates ATP more efficiently than
glycolysis, it has been assumed for many years that
the presence or absence of oxygen determines that
cells generate energy through oxidative
phosphorylation or through glycolysis. Although cells
must activate glycolysis in the absence of oxygen to
produce ATP, it is now accepted that they can activate
both glycolysis and oxidative phosphorylation in the
presence of oxygen. In fact, normal proliferating cells
and tumor cells are known to have a high glycolytic
activity in the presence of adequate oxygen levels, a
phenomenon known as aerobic glycolysis or the
Warburg effect. Recent observations have
demonstrated that the activation of aerobic glycolysis
plays a major role in carcinogenesis and tumor growth.
Understanding the mechanisms involved in the
metabolic switch between oxidative phosphorylation
and aerobic glycolysis may therefore be important for
the development of potential preventive and
therapeutic interventions. In this article, we discuss the
role of the intracellular pH in the metabolic switch
between oxidative phosphorylation and aerobic
glycolysis. We propose that, in the presence of
adequate oxygen levels, the intracellular pH may play
a key role in determining the way cells obtain energy,
an alkaline pH driving aerobic glycolysis and an acidic
pH driving oxidative phosphorylation
