6月15日,，Science在線報(bào)道應(yīng)激相關(guān)激活轉(zhuǎn)錄因子-1進(jìn)入線粒體的效率可調(diào)節(jié)線粒體非折疊蛋白反應(yīng)的水平,。
為了更好地理解線粒體功能障礙的反應(yīng),，研究者研究了,，應(yīng)激相關(guān)激活轉(zhuǎn)錄因子-1（ATFS-1）感受線粒體應(yīng)激過程,，及其在線粒體非折疊蛋白反應(yīng)（UPRmt）條件下與細(xì)胞核通信的機(jī)制,。
研究發(fā)現(xiàn),，調(diào)控的關(guān)鍵點(diǎn)是ATFS-1進(jìn)入線粒體的效率。除了一個(gè)核定位序列,，ATFS-1還有一個(gè)氨基端的線粒體定位序列,。這是UPRmt抑制反應(yīng)所必不可少的。通常情況下,，ATFS-1被導(dǎo)入到線粒體并降解,。然而，在線粒體應(yīng)激情況下,，ATFS-1進(jìn)入線粒體效率下降,，使其相當(dāng)一部分積聚在細(xì)胞質(zhì)并轉(zhuǎn)移到細(xì)胞核中。該研究結(jié)果表明,，細(xì)胞通過ATFS-1監(jiān)測(cè)線粒體蛋白輸入效率,，進(jìn)而利用保護(hù)性轉(zhuǎn)錄反應(yīng)協(xié)調(diào)線粒體功能障礙的水平。（生物谷bioon.com）
doi:10.1016/j.cell.2011.10.017
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Mitochondrial Import Efficiency of ATFS-1 Regulates Mitochondrial UPR Activation
Amrita M. Nargund1,*, Mark W. Pellegrino1,*, Christopher J. Fiorese1,2, Brooke M. Baker1, Cole M. Haynes
To better understand the response to mitochondrial dysfunction, we examined the mechanism by which Activating Transcription Factor associated with Stress-1 (ATFS-1) senses mitochondrial stress and communicates with the nucleus during the mitochondrial unfolded protein response (UPRmt). We found that the key point of regulation was the mitochondrial import efficiency of ATFS-1. In addition to a nuclear localization sequence, ATFS-1 has an amino-terminal mitochondrial targeting sequence, which was essential for UPRmt repression. Normally, ATFS-1 is imported into mitochondria and degraded. However, during mitochondrial stress, import efficiency was reduced, allowing a percentage of ATFS-1 to accumulate in the cytosol and traffic to the nucleus. Our results show that cells monitor mitochondrial import efficiency via ATFS-1 to coordinate the level of mitochondrial dysfunction with the protective transcriptional response
