title: Gene expression of cytokines and cytokine receptors is modulated by the common variability of the mitochondrial DNA in cybrid cell lines.
abstract: Some lines of evidence indicate that common polymorphisms of mitochondrial DNA (mtDNA) act as susceptibility factors in complex traits, such as age-related common diseases. There is also evidence that the cell capability to compensate ravages caused by intrinsic or extrinsic stress factors could contribute to some of these diseases. The cross-talk between nuclear and mitochondrial genome may link the above observations if we assume that the transcription of stress-responder nuclear genes is modulated according to the mtDNA common variability. Cytokines and cytokine receptors are key molecules in stress response. We could, therefore, check the above hypothesis by analyzing expression patterns of cytokine and cytokine receptor genes in response to stress in cell lines sharing the same nuclear genome but different mtDNA. By using a cybrid model (143B.TK- osteosarcoma cells depleted of their own mtDNA and repopulated with foreign mitochondria) we show that the transcription patterns of some of such genes are specifically modulated by the variability of the mitochondrial genome not only under stress conditions (interleukin-6) but also at basal conditions (interleukin-1beta and tumor necrosis factor receptor 2). These findings provide a first experimental evidence of a relationship between mtDNA common variability and expression pattern of stress responder nuclear genes in human cells.
authors.affiliation: Department of Cell Biology, 87030 Rende, University of Calabria, Italy.
authors.forename: Dina
authors.initials: D
authors.lastname: Bellizzi
authors.forename: Paola
authors.initials: P
authors.lastname: Cavalcante
authors.forename: Daniela
authors.initials: D
authors.lastname: Taverna
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Rose
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Passarino
authors.forename: Stefano
authors.initials: S
authors.lastname: Salvioli
authors.forename: Claudio
authors.initials: C
authors.lastname: Franceschi
authors.forename: Giovanna
authors.initials: G
authors.lastname: De Benedictis
mesh_terms: D002459:Cell Fusion; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism*; D004272:DNA, Mitochondrial / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D014644:Genetic Variation; D006801:Humans; D018121:Receptors, Cytokine / Q000378:metabolism*; D013312:Stress, Physiological / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D016207:Cytokines; D004272:DNA, Mitochondrial; D018121:Receptors, Cytokine