Uceda Ana Belén, Donoso Josefa, Frau Juan, Vilanova Bartolomé, Adrover Miquel
Departament de Química, Institut Universitari d'Investigació en Ciències de la Salut (IUNICS), Universitat de les Illes Balears, Ctra. Valldemossa km 7.5, E-07122 Palma de Mallorca, Spain.
Institut d'Investigació Sanitària de les Illes Balears (IdISBa), E-07120 Palma de Mallorca, Spain.
Antioxidants (Basel). 2021 Feb 20;10(2):315. doi: 10.3390/antiox10020315.
Frataxin is a mitochondrial protein which deficiency causes Friedreich's ataxia, a cardio-neurodegenerative disease. The lack of frataxin induces the dysregulation of mitochondrial iron homeostasis and oxidative stress, which finally causes the neuronal death. The mechanism through which frataxin regulates the oxidative stress balance is rather complex and poorly understood. While the absence of human (Hfra) and yeast (Yfh1) frataxins turn out cells sensitive to oxidative stress, this does not occur when the frataxin gene is knocked-out in . To better understand the biological roles of Hfra and Yfh1 as endogenous antioxidants, we have studied their ability to inhibit the formation of reactive oxygen species (ROS) from Cu- and Fe-catalyzed degradation of ascorbic acid. Both proteins drastically reduce the formation of ROS, and during this process they are not oxidized. In addition, we have also demonstrated that merely the presence of Yfh1 or Hfra is enough to protect a highly oxidation-prone protein such as α-synuclein. This unspecific intervention (without a direct binding) suggests that frataxins could act as a shield to prevent the oxidation of a broad set of intracellular proteins, and reinforces that idea that frataxin can be used to prevent neurological pathologies linked to an enhanced oxidative stress.
铁调素是一种线粒体蛋白，其缺乏会导致弗里德赖希共济失调，这是一种心脏神经退行性疾病。铁调素的缺乏会导致线粒体铁稳态失调和氧化应激，最终导致神经元死亡。铁调素调节氧化应激平衡的机制相当复杂，目前了解甚少。虽然缺乏人类（Hfra）和酵母（Yfh1）铁调素会使细胞对氧化应激敏感，但在[此处原文缺失敲除铁调素基因的具体对象]中敲除铁调素基因时却不会出现这种情况。为了更好地理解Hfra和Yfh1作为内源性抗氧化剂的生物学作用，我们研究了它们抑制铜和铁催化抗坏血酸降解产生活性氧（ROS）的能力。这两种蛋白都能大幅减少ROS的形成，并且在此过程中它们不会被氧化。此外，我们还证明，仅仅Yfh1或Hfra的存在就足以保护像α-突触核蛋白这样极易氧化的蛋白质。这种非特异性干预（无直接结合）表明，铁调素可以作为一种屏障来防止多种细胞内蛋白质的氧化，并强化了铁调素可用于预防与氧化应激增强相关的神经病理学的观点。
