The chop gene contains an element for the positive regulation of the mitochondrial unfolded protein response.
We have previously reported on the discovery of a mitochondrial specific unfolded protein response (mtUPR) in mammalian cells, in which the accumulation of unfolded protein within the mitochondrial matrix results in the transcriptional activation of nuclear genes encoding mitochondrial stress proteins such as chaperonin 60, chaperonin 10, mtDnaJ, and ClpP, but not those encoding stress proteins of the endoplasmic reticulum (ER) or the cytosol. Analysis of the chaperonin 60/10 bidirectional promoter showed that the CHOP element was required for the mtUPR and that the transcription of the chop gene is activated by mtUPR. In order to investigate the role of CHOP in the mtUPR, we carried out a deletion analysis of the chop promoter. This revealed that the transcriptional activation of the chop gene by mtUPR is through an AP-1 (activator protein-1) element. This site lies alongside an ERSE element through which chop transcription is activated in response to the ER stress response (erUPR). Thus CHOP can be induced separately in response to 2 different stress response pathways. We also discuss the potential signal pathway between mitochondria and the nucleus for the mtUPR.
Horibe
Tomohisa
T
Department of Biochemistry, La Trobe University, Melbourne, Victoria, Australia.
Hoogenraad
Nicholas J
NJ
D000368:Aged; D000818:Animals; D001483:Base Sequence; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D012689:Sequence Homology, Nucleic Acid; D051742:Transcription Factor CHOP / Q000235:genetics*
C497249:DDIT3 protein, human; C497250:Ddit3 protein, mouse; D051742:Transcription Factor CHOP