Can dietary nitrates enhance the efficiency of mitochondria?

Abstract

A decline in mitochondrial function occurs in many conditions. A report in this issue of Cell Metabolism (Larsen et al., 2011) shows that dietary inorganic nitrates enhance muscle mitochondrial efficiency. It is an attractive hypothesis that dietary changes enhance energy efficiency, but its potential application depends on long-term studies investigating net benefits versus adverse effects.

Figure 1

Mitochondria generate chemical energy (ATP) via the ATP synthase complex, which phosphorylates ADP to ATP using the potential energy provided by the proton gradient across the inner mitochondrial membrane. This proton gradient is maintained by the passage of electrons from reducing equivalents at complexes I and II, converging on co-enzyme Q (Q) into complex III. From there, the mobile electron carrier cytochrome c (C) transfers electrons to complex IV (cytochrome c oxidase) where molecular oxygen is reduced to water. Dissipation of this proton gradient independently of ATP synthesis (i.e., uncoupling) is believed to occur as a result of proton leakage across the inner membrane as well as through various transporters including the adenine nucleotide translocase (ANT) and uncoupling protein 3 (UCP3). ANT exchanges ADP and ATP across the inner membrane and UCP3 are believed to transport fatty acid anions out of the mitochondrial matrix. Dietary nitrates enhance mitochondrial efficiency by reducing the expression of these membrane proteins.