Laboratory of Cellular Biochemistry and Biology, University of Namur, Belgium.
Mitochondria are multifunctional organelles and their maintenance is required for cell homeostasis and function. Upon organelle dysfunction, a mitochondrial-to-nucleus communication, known as retrograde signaling, triggers an orchestrated expression of nuclear genes to relieve the stress and/or compensate the defect. 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.
Host: Prof. Christian Widmann
Haynes, C.M., Fiorese, C.J., Lin, Y.F., 2013. Evaluating and responding to mitochondrial dysfunction: the mitochondrial unfolded-protein response and beyond. Trends in cell biology 23, 311-318.
Michel, S., Canonne, M., Arnould, T., Renard, P., 2015. 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. Mitochondrion 21C, 58-68.