Lewandowska Agnieszka, Gierszewska Magdalena, Marszalek Jaroslaw, Liberek Krzysztof
Department of Molecular and Cellular Biology, Faculty of Biotechnology, University of Gdansk, Kladki 24, 80-822 Gdansk, Poland.
Biochim Biophys Acta. 2006 Feb;1763(2):141-51. doi: 10.1016/j.bbamcr.2006.01.007. Epub 2006 Feb 14.
Under physiological conditions mitochondria of yeast Saccharomyces cerevisiae form a branched tubular network, the continuity of which is maintained by balanced membrane fusion and fission processes. Here, we show using mitochondrial matrix targeted green fluorescent protein that exposure of cells to extreme heat shock led to dramatic changes in mitochondrial morphology, as tubular network disintegrated into several fragmented vesicles. Interestingly, this fragmentation did not affect mitochondrial ability to maintain the membrane potential. Cells subjected to recovery at physiological temperature were able to restore the mitochondrial network, as long as an active matrix chaperone, Hsp78, was present. Deletion of HSP78 gene did not affect fragmentation of mitochondria upon heat stress, but significantly inhibited ability to restore mitochondrial network. Changes of mitochondrial morphology correlated with aggregation of mitochondrial proteins. On the other hand, recovery of mitochondrial network correlated with disappearance of protein aggregates and reactivation of enzymatic activity of a model thermo-sensitive protein: mitochondrial DNA polymerase. Since protein disaggregation and refolding is mediated by Hsp78 chaperone collaborating with Hsp70 chaperone system, we postulate that effect of Hsp78 on mitochondrial morphology upon recovery after heat shock is mediated by its ability to restore activity of unknown protein(s) responsible for maintenance of mitochondrial morphology.
在生理条件下，酿酒酵母的线粒体形成一个分支状的管状网络，其连续性通过平衡的膜融合和裂变过程得以维持。在此，我们利用靶向线粒体基质的绿色荧光蛋白表明，将细胞暴露于极端热休克条件下会导致线粒体形态发生显著变化，管状网络会解体成几个碎片化的囊泡。有趣的是，这种碎片化并不影响线粒体维持膜电位的能力。只要存在活性基质伴侣蛋白Hsp78，在生理温度下进行恢复处理的细胞就能恢复线粒体网络。HSP78基因的缺失并不影响热应激时线粒体的碎片化，但显著抑制了恢复线粒体网络的能力。线粒体形态的变化与线粒体蛋白的聚集相关。另一方面，线粒体网络的恢复与蛋白聚集体的消失以及一种模型热敏蛋白——线粒体DNA聚合酶的酶活性重新激活相关。由于蛋白解聚和重折叠是由Hsp78伴侣蛋白与Hsp70伴侣蛋白系统协同介导的，我们推测热休克后恢复过程中Hsp78对线粒体形态的影响是由其恢复负责维持线粒体形态的未知蛋白活性的能力介导的。
