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

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 mito-chondrial 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 eIF2 alpha/ATF4 axis of the integrated stress response rather than on the mitochondrial unfolded protein response. (C) 2015 Elsevier B.V. and Mitochondria Research Society. All rights reserved.