Sichting Martin, Mokranjac Dejana, Azem Abdussalam, Neupert Walter, Hell Kai
Adolf-Butenandt-Institut, Lehrstuhl für Physiologische Chemie, Ludwig-Maximilians-Universität München, München, Germany.
EMBO J. 2005 Mar 9;24(5):1046-56. doi: 10.1038/sj.emboj.7600580. Epub 2005 Feb 17.
Hsp70 chaperones mediate folding of proteins and prevent their misfolding and aggregation. We report here on a new kind of Hsp70 interacting protein in mitochondria, Hep1. Hep1 is a highly conserved protein present in virtually all eukaryotes. Deletion of HEP1 results in a severe growth defect. Cells lacking Hep1 are deficient in processes that need the function of mitochondrial Hsp70s, such as preprotein import and biogenesis of proteins containing FeS clusters. In the mitochondria of these cells, Hsp70s, Ssc1 and Ssq1 accumulate as insoluble aggregates. We show that it is the nucleotide-free form of mtHsp70 that has a high tendency to self-aggregate. This process is efficiently counteracted by Hep1. We conclude that Hep1 acts as a chaperone that is necessary and sufficient to prevent self-aggregation and to thereby maintain the function of the mitochondrial Hsp70 chaperones.
热休克蛋白70（Hsp70）伴侣蛋白介导蛋白质折叠，防止其错误折叠和聚集。我们在此报告一种存在于线粒体中的新型Hsp70相互作用蛋白——Hep1。Hep1是一种几乎存在于所有真核生物中的高度保守蛋白。HEP1基因缺失会导致严重的生长缺陷。缺乏Hep1的细胞在需要线粒体Hsp70功能的过程中存在缺陷，例如前体蛋白导入以及含FeS簇蛋白的生物合成。在这些细胞的线粒体中，Hsp70蛋白Ssc1和Ssq1会积累形成不溶性聚集体。我们发现，正是无核苷酸形式的线粒体Hsp70具有高度的自我聚集倾向。而这一过程能被Hep1有效抑制。我们得出结论，Hep1作为一种伴侣蛋白，对于防止自我聚集从而维持线粒体Hsp70伴侣蛋白的功能而言是必要且充分的。
