title: Inhibition of mitochondrial genome expression triggers the activation of CHOP-10 by a cell signaling dependent on the integrated stress response but not the mitochondrial unfolded protein response.
abstract: Mitochondria-to-nucleus communication, known as retrograde signaling, is important to adjust the nuclear gene expression in response to organelle dysfunction. Among the transcription factors described to respond to mitochondrial stress, CHOP-10 is activated by respiratory chain inhibition, mitochondrial accumulation of unfolded proteins and mtDNA mutations. In this study, we show that altered/impaired expression of mtDNA induces CHOP-10 expression in a signaling pathway that depends on the eIF2α/ATF4 axis of the integrated stress response rather than on the mitochondrial unfolded protein response.
authors: Laboratory of Biochemistry and Cell Biology (URBC), NAmur Research Institute for LIfe Sciences (NARILIS), University of Namur (UNamur), 61 rue de Bruxelles, 5000 Namur, Belgium.
authors: Sebastien
authors: S
authors: Michel
authors: Laboratory of Biochemistry and Cell Biology (URBC), NAmur Research Institute for LIfe Sciences (NARILIS), University of Namur (UNamur), 61 rue de Bruxelles, 5000 Namur, Belgium.
authors: Morgane
authors: M
authors: Canonne
authors: Laboratory of Biochemistry and Cell Biology (URBC), NAmur Research Institute for LIfe Sciences (NARILIS), University of Namur (UNamur), 61 rue de Bruxelles, 5000 Namur, Belgium.
authors: Thierry
authors: T
authors: Arnould
authors: Laboratory of Biochemistry and Cell Biology (URBC), NAmur Research Institute for LIfe Sciences (NARILIS), University of Namur (UNamur), 61 rue de Bruxelles, 5000 Namur, Belgium. Electronic address: patsy.renard@unamur.be.
authors: Patricia
authors: P
authors: Renard
mesh_terms: D051701:Activating Transcription Factor 4 / Q000378:metabolism; D002460:Cell Line; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D015870:Gene Expression; D054629:Genome, Mitochondrial; D006801:Humans; D015398:Signal Transduction; D013312:Stress, Physiological; D051742:Transcription Factor CHOP / Q000378:metabolism*; D056811:Unfolded Protein Response
chemical_list: C497109:ATF4 protein, human; C497249:DDIT3 protein, human; D015852:Eukaryotic Initiation Factor-2; D051701:Activating Transcription Factor 4; D051742:Transcription Factor CHOP
keywords: C/EBP homologous protein 10 (CHOP-10); Doxycycline; Integrated stress response (ISR); Mitochondria unfolded protein response (mtUPR); Mitochondrial dysfunction; mtDNA depletion