LOSS OF MITOCHONDRIAL HSP60 FUNCTION - NONEQUIVALENT EFFECTS ON MATRIX-TARGETED AND INTERMEMBRANE-TARGETED PROTEINS
LOSS OF MITOCHONDRIAL HSP60 FUNCTION - NONEQUIVALENT EFFECTS ON MATRIX-TARGETED AND INTERMEMBRANE-TARGETED PROTEINS
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DOI：
10.1128/mcb.13.5.3050
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发表时间：
1993-05-01
影响因子：
5.3
通讯作者：
HALLBERG, RL
中科院分区：
文献类型：
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作者：
HALLBERG, EM;SHU, YM;HALLBERG, RL
我们已经创建了酵母菌株，其中线粒体伴侣蛋白hsp60可以物理耗尽或功能失活。完全耗尽hsp60的细胞停止生长，但保留一段时间重新积累hsp60的能力。虽然这种新产生的hsp60是针对和正确处理内的functional hsp60复合物的组装不会发生。相反，热休克蛋白60单体定位在不同大小的可溶性复合物含有另一个线粒体伴侣，线粒体形式的热休克蛋白70。在没有功能性hsp60的情况下合成的许多其他线粒体基质靶向蛋白质被导入线粒体，但通常显示出一些前体形式的积累，并且与hsp60不同，积累为不溶性聚集体。相比之下，几个线粒体蛋白质通常针对膜间隙显示正常的加工完全没有一个功能性的热休克蛋白60复合物。当我们研究表达三种不同的温度敏感的HSP 60等位基因的细胞中基质和膜间空间定位蛋白的代谢时，得到了类似和互补的结果。在所有情况下，基质靶向蛋白质在非允许条件下合成（即，Hsp60失活）温度正确地靶向线粒体并在线粒体内加工，但主要或全部作为不溶性聚集体积累。两个膜间空间蛋白，细胞色素b2和细胞色素c1的代谢，不受影响，在非允许的温度下，正确的处理和新合成的两种蛋白质的形式的完全溶解度的判断。这些研究结果进行了讨论，关于目前的模型膜间靶向。
We have created yeast strains in which the mitochondrial chaperonin, hsp60, can be either physically depleted or functionally inactivated. Cells completely depleted of hsp60 stop growing but retain for awhile the capacity to reaccumulate hsp60. While this newly made hsp60 is targeted to and processed correctly within the mitochondrion, assembly of a functional hsp60 complex does not occur. Rather, the hsp60 monomers are localized in different-size soluble complexes containing another mitochondrial chaperone, the mitochondrial form of hsp70. A number of other mitochondrial matrix-targeted proteins synthesized in the absence of functional hsp60 are imported into mitochondria but often show some buildup of precursor forms and, unlike hsp60, accumulate as insoluble aggregates. By contrast, several mitochondrial proteins normally targeted to the intermembrane space show normal processing in the complete absence of a functional hsp60 complex. Similar and complementary results were obtained when we examined the metabolism of matrix- and intermembrane space-localized proteins in cells expressing three different temperature-sensitive alleles of HSP60. In all cases, matrix-targeted proteins synthesized at nonpermissive (i.e., hsp60-inactivating) temperatures were correctly targeted to and processed within mitochondria but accumulated predominantly or totally as insoluble aggregates. The metabolism of two intermembrane space proteins, cytochrome b2 and cytochrome c1, was unaffected at the nonpermissive temperature, as judged by the correct processing and complete solubility of newly synthesized forms of both proteins. These findings are discussed with regard to current models of intermembrane targeting.