Interference with plastome gene expression and Clp protease activity in Arabidopsis triggers a chloroplast unfolded protein response to restore protein homeostasis.
Interference with plastome gene expression and Clp protease activity in Arabidopsis triggers a chloroplast unfolded protein response to restore protein homeostasis.
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DOI：
10.1371/journal.pgen.1007022
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发表时间：
2017-09
期刊：
影响因子：
4.5
通讯作者：
Rodriguez-Concepcion M
中科院分区：
文献类型：
--
作者：
Llamas E;Pulido P;Rodriguez-Concepcion M
叶绿体中蛋白质稳态的破坏损害了基本代谢途径的正确功能，包括用于产生参与光合作用和生长的质体类异戊二烯的甲基β 4-磷酸（MEP）途径。我们以前发现，MEP途径的第一种酶的错误折叠和聚集形式被Clp蛋白酶降解，并参与拟南芥中的Hsp 70和Hsp 100/ClpC 1分子伴侣。相比之下，Hsp 70和Hsp 100/ClpB 3分子伴侣的组合解折叠和解聚作用允许酶的溶解并因此再活化。当用叶绿体蛋白合成抑制剂林可霉素（LIN）处理的突变体或野生型植物中Clp蛋白酶活性降低时，ClpB 3蛋白的水平增加时，修复途径得到促进。在这里，我们表明，LIN处理迅速增加了叶绿体中聚集蛋白的水平，释放出一个特定的逆行信号通路，上调ClpB 3和其他核基因编码质体伴侣蛋白的表达。因此，折叠能力增加以恢复蛋白质稳态。这种叶绿体未折叠蛋白反应（cpUPR）机制似乎是由热休克转录因子HsfA 2介导的。HsfA 2和cpUPR相关靶基因的表达不依赖于GUN 1，GUN 1是逆行信号通路的中心整合者。然而，GUN 1和质体基因表达（或Clp蛋白酶活性）均缺陷的双突变体对幼苗是致命的，这证实了GUN 1蛋白对于叶绿体中的蛋白质稳态至关重要。叶绿体是植物细胞的核心代谢工厂。然而，它们不断受到改变蛋白质稳态和破坏正常叶绿体功能的压力事件的挑战。为了解决这个问题，涉及特定分子伴侣和蛋白酶的蛋白质质量控制途径促进正确的蛋白质折叠并去除不可逆损伤的蛋白质。在DXS（类异戊二烯途径的主要调节酶）的情况下，酶的错误折叠和聚集形式通过Hsp 70和Hsp 100/ClpB家族的基质伴侣蛋白重折叠回其活性形式，从而防止它们被Clp蛋白酶复合物降解。在本文中，我们报告说，饱和或有缺陷的Clp蛋白酶活性触发叶绿体未折叠的蛋白质的反应，导致核基因编码的叶绿体伴侣的上调。当Clp蛋白酶活性和叶绿体功能受损时，较高水平的这些分子伴侣（特别是解聚酶ClpB 3）最终恢复DXS和以非功能形式积累的其他叶绿体蛋白的活性。
Disruption of protein homeostasis in chloroplasts impairs the correct functioning of essential metabolic pathways, including the methylerythritol 4-phosphate (MEP) pathway for the production of plastidial isoprenoids involved in photosynthesis and growth. We previously found that misfolded and aggregated forms of the first enzyme of the MEP pathway are degraded by the Clp protease with the involvement of Hsp70 and Hsp100/ClpC1 chaperones in Arabidopsis thaliana. By contrast, the combined unfolding and disaggregating actions of Hsp70 and Hsp100/ClpB3 chaperones allow solubilization and hence reactivation of the enzyme. The repair pathway is promoted when the levels of ClpB3 proteins increase upon reduction of Clp protease activity in mutants or wild-type plants treated with the chloroplast protein synthesis inhibitor lincomycin (LIN). Here we show that LIN treatment rapidly increases the levels of aggregated proteins in the chloroplast, unleashing a specific retrograde signaling pathway that up-regulates expression of ClpB3 and other nuclear genes encoding plastidial chaperones. As a consequence, folding capacity is increased to restore protein homeostasis. This sort of chloroplast unfolded protein response (cpUPR) mechanism appears to be mediated by the heat shock transcription factor HsfA2. Expression of HsfA2 and cpUPR-related target genes is independent of GUN1, a central integrator of retrograde signaling pathways. However, double mutants defective in both GUN1 and plastome gene expression (or Clp protease activity) are seedling lethal, confirming that the GUN1 protein is essential for protein homeostasis in chloroplasts. Chloroplasts are central metabolic factories for plant cells. Yet, they are constantly challenged by stress episodes that alter protein homeostasis and disrupt normal chloroplast functions. To deal with this problem, protein quality control pathways involving particular chaperones and proteases promote correct protein folding and remove irreversibly damaged proteins. In the case of DXS, the main regulatory enzyme of the isoprenoid pathway, misfolded and aggregated forms of the enzyme are refolded back to its active form by stromal chaperones of the Hsp70 and Hsp100/ClpB families, hence preventing their degradation by the Clp protease complex. In this paper we report that saturated or defective Clp protease activity triggers a chloroplast unfolded protein response that results in the up-regulation of nuclear genes encoding chloroplast chaperones. Higher levels of these chaperones (particularly the disaggregase ClpB3) eventually restore the activity of DXS and other chloroplast proteins that accumulate in a non-functional form when Clp protease activity and chloroplast functions are compromised.
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影响因子：
7.4
作者：
Lee, GJ;Vierling, E
通讯作者：
Vierling, E
影响因子：
11.8
作者：
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影响因子：
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作者：
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通讯作者：
FINKELSTEIN, RR
DOI：
10.1073/pnas.1602582113
发表时间：
2016-08-02
影响因子：
11.1
作者：
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通讯作者：
Dehesh, Katayoon
影响因子：
5.1
作者：
Carretero-Paulet, Lorenzo;Cairo, Albert;Rodriguez-Concepcion, Manuel
通讯作者：
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