title: The antioxidant function of Bcl-2 preserves cytoskeletal stability of cells with defective respiratory complex I.
abstract: Human thyroid carcinoma XTC.UC1 cells harbor a homoplasmic frameshift mutation in the MT-ND1 subunit of respiratory complex I. When forced to use exclusively oxidative phosphorylation for energy production by inhibiting glycolysis, these cells triggered a caspase-independent cell death pathway, which was associated to a significant imbalance in glutathione homeostasis and a cleavage of the actin cytoskeleton. Overexpression of the anti-apoptotic Bcl-2 protein significantly increased the level of endogenous reduced glutathione, thus preventing its oxidation after the metabolic stress. Furthermore, Bcl-2 completely inhibited actin cleavage and increased cell adhesion, but was unable to improve cellular viability. Similar effects were obtained when XTC.UC1 cells were incubated with exogenous glutathione. We hence propose that Bcl-2 can safeguard cytoskeletal stability through an antioxidant function.
authors.affiliation: Dipartimento di Biologia Evoluzionistica Sperimentale, Università di Bologna, Via Irnerio 42, Bologna 40122, Italy. annamaria.porcelli@unibo.it
authors.forename: A M
authors.initials: AM
authors.lastname: Porcelli
authors.forename: A
authors.initials: A
authors.lastname: Ghelli
authors.forename: L
authors.initials: L
authors.lastname: Iommarini
authors.forename: E
authors.initials: E
authors.lastname: Mariani
authors.forename: M
authors.initials: M
authors.lastname: Hoque
authors.forename: C
authors.initials: C
authors.lastname: Zanna
authors.forename: G
authors.initials: G
authors.lastname: Gasparre
authors.forename: M
authors.initials: M
authors.lastname: Rugolo
mesh_terms: D000199:Actins / Q000378:metabolism; D000975:Antioxidants / Q000378:metabolism*; D045744:Cell Line, Tumor; D048430:Cell Shape; D003599:Cytoskeleton / Q000378:metabolism*; D042967:Electron Transport Complex I / Q000502:physiology*; D005978:Glutathione / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D009154:Mutation; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D013964:Thyroid Neoplasms
chemical_list: D000199:Actins; D000975:Antioxidants; D021122:Protein Subunits; D019253:Proto-Oncogene Proteins c-bcl-2; D042967:Electron Transport Complex I; D005978:Glutathione