Dimethyl Fumarate Mediates Nrf2-dependent Mitochondrial Biogenesis in Mice and Humans

Genki Hayashi, Mittal Jasoliya, Francesco Saccà, Chiara Pane, Alessandro Filla, Angela Marsili, Giorgia Puorro, Roberta Lanzillo, Vincenzo Brescia Morra, Gino Cortopassi; Hum Mol Genet 2017 ddx167. doi: 10.1093/hmg/ddx167

The induction of mitochondrial gene expression is more dependent on its target Nrf2 than hydroxycarboxylic acid receptor 2 (HCAR2). Thus, DMF induces mitochondrial biogenesis primarily through its action on Nrf2, and is the first drug demonstrated to increase mitochondrial biogenesis with in vivo human dosing. The observation that DMF stimulates mitochondrial biogenesis, gene expression and function suggests that it could be considered for mitochondrial disease therapy and/or therapy in muscle disease in which mitochondrial function is important.