title: Mitofusin 2 Deficiency Affects Energy Metabolism and Mitochondrial Biogenesis in MEF Cells.
abstract: Mitofusin 2 (Mfn2), mitochondrial outer membrane protein which is involved in rearrangement of these organelles, was first described in pathology of hypertension and diabetes, and more recently much attention is paid to its functions in Charcot-Marie-Tooth type 2A neuropathy (CMT2A). Here, cellular energy metabolism was investigated in mouse embryonic fibroblasts (MEF) differing in the presence of the Mfn2 gene; control (MEFwt) and with Mfn2 gene depleted MEFMfn2-/-. These two cell lines were compared in terms of various parameters characterizing mitochondrial bioenergetics. Here, we have shown that relative rate of proliferation of MEFMfn2-/- cells versus control fibroblasts depend on serum supplementation of the growth media. Moreover, MEFMfn2-/- cells exhibited significantly increased respiration rate in comparison to MEFwt, regardless of serum supplementation of the medium. This effect was correlated with increased level of mitochondrial markers (TOM20 and NAO) as well as mitochondrial transcription factor A (TFAM) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) protein levels and unchanged total ATP content. Interestingly, mitochondrial DNA content in MEFMfn2-/- cells was not reduced. Fundamentally, these results are in contrast to a commonly accepted belief that mitofusin 2 deficiency inevitably results in debilitation of mitochondrial energy metabolism. However, we suggest a balance between negative metabolic consequences of mitofusin 2 deficiency and adaptive processes exemplified by increased level of PGC-1α and TFAM transcription factor which prevent an excessive depletion of mtDNA and severe impairment of cell metabolism.
authors.affiliation: Molecular Biology Unit, Mossakowski Medical Research Centre, PAS, Warsaw, Poland.
authors.forename: Maria
authors.initials: M
authors.lastname: Kawalec
authors.affiliation: Molecular Biology Unit, Mossakowski Medical Research Centre, PAS, Warsaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Boratyńska-Jasińska
authors.affiliation: Molecular Biology Unit, Mossakowski Medical Research Centre, PAS, Warsaw, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Beręsewicz
authors.affiliation: Department of Biochemistry, Nencki Institute of Experimental Biology, PAS, Warsaw, Poland.
authors.forename: Dorota
authors.initials: D
authors.lastname: Dymkowska
authors.affiliation: Department of Biochemistry, Nencki Institute of Experimental Biology, PAS, Warsaw, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Zabłocki
authors.affiliation: Molecular Biology Unit, Mossakowski Medical Research Centre, PAS, Warsaw, Poland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Zabłocka
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D004734:Energy Metabolism; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000502:physiology*; D053078:Membrane Potential, Mitochondrial; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*
chemical_list: D020558:GTP Phosphohydrolases; C488751:Mfn2 protein, mouse