Dimethyl fumarate mediates Nrf2-dependent mitochondrial biogenesis in mice and humans

The induction of mitochondrial biogenesis could potentially alleviate mitochondrial and muscle disease. We show here that dimethyl fumarate (DMF) dose-dependently induces mitochondrial biogenesis and function dosed to cells in vitro, and also dosed in vivo to mice and humans. The induction of mitoch...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Human molecular genetics Jg. 26; H. 15; S. 2864
Hauptverfasser: Hayashi, Genki, Jasoliya, Mittal, Sahdeo, Sunil, Saccà, Francesco, Pane, Chiara, Filla, Alessandro, Marsili, Angela, Puorro, Giorgia, Lanzillo, Roberta, Brescia Morra, Vincenzo, Cortopassi, Gino
Format: Journal Article
Sprache:Englisch
Veröffentlicht: England 01.08.2017
Schlagworte:
Animals
Cell Culture Techniques
Dimethyl Fumarate - chemistry
Dimethyl Fumarate - metabolism
Fibroblasts
Humans
Mice
Mitochondria - metabolism
Multiple Sclerosis - metabolism
Multiple Sclerosis - pathology
Neuroprotective Agents - pharmacology
NF-E2-Related Factor 2 - genetics
NF-E2-Related Factor 2 - metabolism
Organelle Biogenesis
ISSN:1460-2083, 1460-2083
Online-Zugang:Weitere Angaben
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:The induction of mitochondrial biogenesis could potentially alleviate mitochondrial and muscle disease. We show here that dimethyl fumarate (DMF) dose-dependently induces mitochondrial biogenesis and function dosed to cells in vitro, and also dosed in vivo to mice and humans. The induction of mitochondrial gene expression is more dependent on DMF's 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. This is the first demonstration that mitochondrial biogenesis is deficient in Multiple Sclerosis patients, which could have implications for MS pathophysiology and therapy. 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.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1460-2083
1460-2083
DOI:10.1093/hmg/ddx167