线粒体在细胞功能中起关键作用，包括能量生产和氧化应激调节。出于这个原因,维持线粒体稳态和蛋白质组稳态（蛋白质组的稳态）对于细胞健康至关重要。因此,有不同的线粒体质量控制机制，比如线粒体生物发生，线粒体动力学，线粒体来源的囊泡（MDV），线粒体自噬,或线粒体未折叠蛋白反应（mtUPR）。最后一项是当线粒体内存在压力时发生的应激反应，尤其是,当线粒体基质中未折叠和错误折叠蛋白质的积累超过线粒体的折叠能力时。对此,分子伴侣和蛋白酶以及线粒体抗氧化系统被激活，以恢复线粒体蛋白稳定和细胞功能。在疾病背景下，mtUPR调节通过减轻线粒体功能障碍保持治疗潜力。特别是,在神经退行性疾病的情况下，例如原发性线粒体疾病，阿尔茨海默病（AD），帕金森病（PD），亨廷顿病（HD），肌萎缩侧索硬化(ALS),或弗里德里希的共济失调(FA)，有大量证据表明,在各种细胞和动物模型中,mtUPR的调节有助于减少神经变性及其相关症状.这些发现强调了mtUPR在对抗这些破坏性疾病中作为一个有希望的治疗靶点的作用。
Mitochondria play a key role in cellular functions, including energy production and oxidative stress regulation. For this reason, maintaining mitochondrial homeostasis and proteostasis (homeostasis of the proteome) is essential for cellular health. Therefore, there are different mitochondrial quality control mechanisms, such as mitochondrial biogenesis, mitochondrial dynamics, mitochondrial-derived vesicles (MDVs), mitophagy, or mitochondrial unfolded protein response (mtUPR). The last item is a stress response that occurs when stress is present within mitochondria and, especially, when the accumulation of unfolded and misfolded proteins in the mitochondrial matrix surpasses the folding capacity of the mitochondrion. In response to this, molecular chaperones and proteases as well as the mitochondrial antioxidant system are activated to restore mitochondrial proteostasis and cellular function. In disease contexts, mtUPR modulation holds therapeutic potential by mitigating mitochondrial dysfunction. In particular, in the case of neurodegenerative diseases, such as primary mitochondrial diseases, Alzheimer\'s disease (AD), Parkinson\'s disease (PD), Huntington\'s disease (HD), Amyotrophic Lateral Sclerosis (ALS), or Friedreich\'s Ataxia (FA), there is a wealth of evidence demonstrating that the modulation of mtUPR helps to reduce neurodegeneration and its associated symptoms in various cellular and animal models. These findings underscore mtUPR\'s role as a promising therapeutic target in combating these devastating disorders.
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