Functional Significance of the Mitochondrial Membrane Potential

The electrical polarization of the inner mitochondrial membrane largely determines the electrochemical potential of hydrogen ifons, being thereby a significant factor in the energy transformation during oxidation of respiratory substrates and its accumulation in the form of newly synthesized ATP. However, the gradient of the electric potential on the inner mitochondrial membrane (ΔΨm) performs a number of functions not related to energy production. Even under hypoxic conditions, precluding the formation of ATP in mitochondria through oxidative phosphorylation, mitochondria maintain their ΔΨm at the expense of the hydrolysis of cellular ATP, which indicates the exceptional importance of ΔΨm for non-energetic functions of mitochondria. Among these functions, the mitochondrial inward transport of metal cations and proteins carrying a positively charged amino acid sequence and export of anions including nucleic acids possibly providing retrograde signaling, seem very important and essential for maintaining mitochondrial structure and metabolism. ΔΨm is a powerful regulator of mitochondrial generation of reactive oxygen species that perform physiological and pathological functions. And finally, ΔΨm is a critical element in the mechanism of disposal of dysfunctional mitochondria, the so-called quality control machinery of mitochondria. The disturbance of this mechanism leads to increase of heterogeneity in the population of mitochondria in the cell, and the degree of heterogeneity can be considered as an indicator of the pathological cellular phenotype. Correlation between Ψm and cell functions is difficult to identify without adequate quantitative estimates of the magnitude of ΔΨm, which are complicated due to several cellular and mitochondrial processes that affect the experimentally obtained values. Recommendations for assessing the contribution of these processes and avoiding artifacts in the measurements of ΔΨm by standard methods are given.