Nitrite protects mitochondrial structure and function under hypoxia

Abstract

Oxygen deprivation leads to changes in mitochondrial morphology and impaired flow of reducing equivalents through the electron transport chain. The extent of these changes depends on the duration and severity of the treatment as well as on the species and cell type. Nitrate is known to ameliorate these effects in some instances, but it is possible that it is nitrite, rather than nitrate, that is the key to the mechanism. To test this, mitochondria were isolated from 21-day-old pea (Pisum sativum) roots and incubated for 90min under normoxia or hypoxia in the presence or absence of 0.5 mM nitrite. The supply of nitrite under hypoxia led to nitric oxide production, improved mitochondrial integrity, improved energization of the inner mitochondrial membrane, increased ATP synthesis, decreased production of reactive oxygen species and decreased lipid peroxidation. It also resulted in higher levels and activities of complex I and the supercomplex I + III2. It is concluded that nitrite has an important role in maintaining mitochondrial function under hypoxia, and that it achieves this through the reduction of nitrite to nitric oxide by the mitochondrial electron transport chain.