Department of Biochemistry, La Trobe University, Melbourne, Victoria, Australia.
PLoS One. 2007 Sep 12;2(9):e835. doi: 10.1371/journal.pone.0000835.
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.
我们之前曾报道过在哺乳动物细胞中线粒体特异性未折叠蛋白反应（mtUPR）的发现，其中线粒体基质中未折叠蛋白的积累导致核基因的转录激活，这些核基因编码线粒体应激蛋白，如伴侣蛋白 60、伴侣蛋白 10、mtDnaJ 和 ClpP，但不编码内质网（ER）或细胞质中的应激蛋白。对伴侣蛋白 60/10 双向启动子的分析表明，CHOP 元件是 mtUPR 所必需的，并且 chop 基因的转录被 mtUPR 激活。为了研究 CHOP 在 mtUPR 中的作用，我们对 chop 启动子进行了缺失分析。这表明 mtUPR 通过 AP-1（激活蛋白-1）元件激活 chop 基因的转录。该位点与 ERSE 元件相邻，通过该元件，chop 转录在 ER 应激反应（erUPR）中被激活。因此，CHOP 可以分别响应 2 种不同的应激反应途径被诱导。我们还讨论了 mtUPR 中线粒体和核之间的潜在信号通路。
