title: Resveratrol stimulates mitochondrial fusion by a mechanism requiring mitofusin-2.
abstract: Resveratrol (RES) is a plant-derived stilbene associated with a wide range of health benefits. Mitochondria are a key downstream target of RES, and in some cell types RES promotes mitochondrial biogenesis, altered cellular redox status, and a shift toward oxidative metabolism. Mitochondria exist as a dynamic network that continually remodels via fusion and fission processes, and the extent of fusion is related to cellular redox status and metabolism. We investigated RES's effects on mitochondrial network morphology in several cell lines using a quantitative approach to measure the extent of network fusion. 48 h continuous treatment with 10-20 μM RES stimulated mitochondrial fusion in C2C12 myoblasts, PC3 cancer cells, and mouse embryonic fibroblasts stimulated significant increases in fusion in all instances, resulting in larger and more highly branched mitochondrial networks. Mitofusin-2 (Mfn2) is a key protein facilitating mitochondrial fusion, and its expression was also stimulated by RES. Using Mfn2-null cells we demonstrated that RES's effects on mitochondrial fusion, cellular respiration rates, and cell growth are all dependent upon the presence of Mfn2. Taken together, these results demonstrate that Mfn2 and mitochondrial fusion are affected by RES in ways that appear to relate to RES's known effects on cellular metabolism and growth.
authors.affiliation: Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, L8S 4L8, Canada.
authors.forename: Ellen L
authors.initials: EL
authors.lastname: Robb
authors.affiliation: Department of Biological Sciences, Brock University, St. Catharines, L2S 3A1, Ontario, Canada.
authors.forename: Fereshteh
authors.initials: F
authors.lastname: Moradi
authors.affiliation: Department of Biological Sciences, Brock University, St. Catharines, L2S 3A1, Ontario, Canada.
authors.forename: Lucas A
authors.initials: LA
authors.lastname: Maddalena
authors.affiliation: Department of Biological Sciences, Brock University, St. Catharines, L2S 3A1, Ontario, Canada.
authors.forename: Andrew J F
authors.initials: AJF
authors.lastname: Valente
authors.affiliation: Department of Biological Sciences, Brock University, St. Catharines, L2S 3A1, Ontario, Canada.
authors.forename: Joao
authors.initials: J
authors.lastname: Fonseca
authors.affiliation: Department of Biological Sciences, Brock University, St. Catharines, L2S 3A1, Ontario, Canada. Electronic address: jstuart@brocku.ca.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Stuart
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D063154:Mitochondrial Dynamics / Q000187:drug effects*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D024101:Mitochondrial Proteins; D013267:Stilbenes; D020558:GTP Phosphohydrolases; C470018:MFN2 protein, human; C488751:Mfn2 protein, mouse; D000077185:Resveratrol
keywords: Cell proliferation; Fusion; Mitochondria; Mitofusin 2; Resveratrol