Nrf2 impacts the efficiency of mitochondrial fatty acid oxidation

Transcription factor NF-E2 p45-related factor 2 (Nrf2) regulates the cellular redox homeostasis and cytoprotective responses, allowing adaptation and survival under conditions of stress. The significance of Nrf2 in intermediary metabolism is also beginning to be recognized. Thus, this transcription factor affects negatively fatty acid synthesis. However the effect of Nrf2 on fatty acid oxidation is presently unknown. We now report that the mitochondrial oxidation of long-(palmitic) and short-(hexanoic) chain fatty acids is depressed in the absence of Nrf2 and accelerated when Nrf2 is constitutively active. Addition of fatty acids stimulates respiration in heart and liver mitochondria isolated from wild-type mice. This effect is significantly weaker when Nrf2 is deleted, whereas it is stronger when Nrf2 activity is constitutively high. In the absence of glucose, addition of fatty acids differentially affects the production of ATP in mouse embryonic fibroblasts from wild-type, Nrf2-knockout and Keap1-knockout mice. In acute tissue slices, the rate of regeneration of FADH2 is reduced when Nrf2 is absent. This metabolic role of Nrf2 on fatty acid oxidation has implications for chronic disease conditions including cancer, metabolic syndrome and neurodegeneration.
Source: BJ Cell - Category: Biochemistry Authors: Tags: BJ Metabolism Source Type: research