Laboratory of Cell and Developmental Genetics, Department of Molecular Biology, Medical Biochemistry and Pathology, Institut de Biologie Intégrative et des Systèmes and PROTEO Université Laval, Québec, Canada.
Ann N Y Acad Sci. 2010 Jun;1197:67-75. doi: 10.1111/j.1749-6632.2009.05413.x.
Aging is a complex process accompanied by a decreased capacity of cells to cope with random molecular damages. Damaged proteins can form aggregates and have cytotoxic properties, a feature of many age-associated diseases. Small Hsps are chaperones involved in the refolding and/or disposal of protein aggregates. In Drosophila melanogaster, the mitochondrial DmHsp22 is preferentially upregulated during aging. Its over-expression results in an extension of lifespan (>30%) and an increased resistance to stress. Although DmHsp22 has a chaperone-like activity in vitro, additional mechanisms by which it may extend lifespan in vivo are unknown. Genome-wide transcriptional analysis and comparative mitochondrial proteomic analysis by MALDI-TOF were performed to unveil differences in long-lived DmHsp22 over-expressing flies. Flies over-expressing DmHsp22 display an upregulation of genes normally downregulated with age and involved in energy production and protein biosynthesis. Interestingly, DmHsp22 over-expression extended lifespan of normal fibroblasts by slowing the aging process. However, its expression also increased the malignant properties of human transformed cells. The delicate balance between beneficial and noxious effects of this small chaperone are discussed.
衰老是一个复杂的过程，伴随着细胞应对随机分子损伤的能力下降。受损的蛋白质可以形成聚集体，并具有细胞毒性，这是许多与年龄相关的疾病的特征。小分子热休克蛋白是参与蛋白质聚集体重折叠和/或处理的伴侣分子。在黑腹果蝇中，线粒体 DmHsp22 在衰老过程中优先上调。其过表达导致寿命延长（>30%）和应激抗性增加。尽管 DmHsp22 在体外具有伴侣样活性，但尚不清楚它在体内延长寿命的其他机制。进行了全基因组转录分析和 MALDI-TOF 的比较线粒体蛋白质组分析，以揭示长寿 DmHsp22 过表达果蝇的差异。过表达 DmHsp22 的果蝇显示出与年龄相关的下调基因的上调，这些基因参与能量产生和蛋白质生物合成。有趣的是，DmHsp22 的过表达通过减缓衰老过程延长了正常成纤维细胞的寿命。然而，它的表达也增加了人转化细胞的恶性特性。讨论了这种小分子伴侣的有益和有害作用之间的微妙平衡。
