Laboratory for Integrative and Systems Physiology, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne CH-1015, Switzerland.
J Exp Biol. 2014 Jan 1;217(Pt 1):137-43. doi: 10.1242/jeb.090738.
The ability to respond to various intracellular and/or extracellular stresses allows the organism to adapt to changing environmental conditions and drives evolution. It is now well accepted that a progressive decline of the efficiency of stress response pathways occurs with aging. In this context, a correct proteostasis is essential for the functionality of the cell, and its dysfunction has been associated with protein aggregation and age-related degenerative diseases. Complex response mechanisms have evolved to deal with unfolded protein stress in different subcellular compartments and their moderate activation translates into positive effects on health. In this review, we focus on the mitochondrial unfolded protein response (UPR(mt)), a response to proteotoxic stress specifically in mitochondria, an organelle with a wide array of fundamental functions, most notably the harvesting of energy from food and the control of cell death. We compare UPR(mt) with the extensively characterized cytosolic heat shock response (HSR) and the unfolded protein response in endoplasmic reticulum (UPR(ER)), and discuss the current knowledge about UPR(mt) signaling pathways as well as their potential involvement in physiology.
生物体能够对各种细胞内和/或细胞外应激做出反应，从而适应不断变化的环境条件，并推动进化。现在人们已经充分认识到，随着年龄的增长，应激反应途径的效率会逐渐下降。在这种情况下，正确的蛋白质稳态对于细胞的功能至关重要，其功能障碍与蛋白质聚集和与年龄相关的退行性疾病有关。为了应对不同亚细胞区室中未折叠蛋白的应激，已经进化出了复杂的反应机制，而其适度的激活会对健康产生积极影响。在这篇综述中，我们重点介绍了线粒体未折叠蛋白反应（UPR(mt)），这是一种专门针对线粒体中蛋白毒性应激的反应，线粒体是一种具有广泛基本功能的细胞器，其最重要的功能是从食物中获取能量和控制细胞死亡。我们将 UPR(mt)与广泛研究的胞质热休克反应（HSR）和内质网中的未折叠蛋白反应（UPR(ER)）进行了比较，并讨论了目前关于 UPR(mt)信号通路的知识及其在生理学中的潜在作用。
