Favia Maria, de Bari Lidia, Bobba Antonella, Atlante Anna
Istituto di Biomembrane, Bioenergetica e Biotecnologie Molecolari -CNR, Via G. Amendola 122/O, 70126 Bari, Italy.
Dipartimento di Bioscienze, Biotecnologie e Biofarmaceutica, Università di Bari, Via E. Orabona 4, 70126 Bari, Italy.
J Clin Med. 2019 Nov 6;8(11):1890. doi: 10.3390/jcm8111890.
Cystic fibrosis (CF) occurs when the cystic fibrosis transmembrane conductance regulator (CFTR) protein is not synthetized and folded correctly. The CFTR protein helps to maintain the balance of salt and water on many body surfaces, such as the lung surface. When the protein is not working correctly, chloride becomes trapped in cells, then water cannot hydrate the cellular surface and the mucus covering the cells becomes thick and sticky. Furthermore, a defective CFTR appears to produce a redox imbalance in epithelial cells and extracellular fluids and to cause an abnormal generation of reactive oxygen species: as a consequence, oxidative stress has been implicated as a causative factor in the aetiology of the process. Moreover, massive evidences show that defective CFTR gives rise to extracellular GSH level decrease and elevated glucose concentrations in airway surface liquid (ASL), thus encouraging lung infection by pathogens in the CF advancement. Recent research in progress aims to rediscover a possible role of mitochondria in CF. Here the latest new and recent studies on mitochondrial bioenergetics are collected. Surprisingly, they have enabled us to ascertain that mitochondria have a leading role in opposing the high ASL glucose level as well as oxidative stress in CF.
当囊性纤维化跨膜传导调节因子（CFTR）蛋白无法正确合成和折叠时，就会发生囊性纤维化（CF）。CFTR蛋白有助于维持许多身体表面（如肺表面）的盐和水平衡。当该蛋白无法正常工作时，氯离子会被困在细胞中，随后水无法为细胞表面提供水合作用，覆盖细胞的黏液会变得浓稠且黏腻。此外，有缺陷的CFTR似乎会在上皮细胞和细胞外液中产生氧化还原失衡，并导致活性氧的异常生成：因此，氧化应激被认为是该疾病病因中的一个致病因素。此外，大量证据表明，有缺陷的CFTR会导致细胞外谷胱甘肽水平降低以及气道表面液体（ASL）中的葡萄糖浓度升高，从而在CF进展过程中促使病原体引发肺部感染。目前正在进行的研究旨在重新发现线粒体在CF中的可能作用。在此收集了关于线粒体生物能量学的最新和近期研究。令人惊讶的是，这些研究使我们能够确定线粒体在对抗CF中高ASL葡萄糖水平以及氧化应激方面起着主导作用。
