De Lazzari Federica, Agostini Francesco, Doni Davide, Malacrida Sandro, Zordan Mauro A, Costantini Paola, Bubacco Luigi, Sandrelli Federica, Bisaglia Marco
Department of Biology, University of Padova, Via Ugo Bassi 58/B, 35131 Padova, Italy.
Medical Research Council, Mitochondria Biology Unit, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0XY, UK.
Antioxidants (Basel). 2022 Aug 5;11(8):1527. doi: 10.3390/antiox11081527.
Redox homeostasis is a vital process the maintenance of which is assured by the presence of numerous antioxidant small molecules and enzymes and the alteration of which is involved in many pathologies, including several neurodegenerative disorders. Among the different enzymes involved in the antioxidant response, SOD1 and DJ-1 have both been associated with the pathogenesis of amyotrophic lateral sclerosis and Parkinson's disease, suggesting a possible interplay in their mechanism of action. Copper deficiency in the SOD1-active site has been proposed as a central determinant in SOD1-related neurodegeneration. SOD1 maturation mainly relies on the presence of the protein copper chaperone for SOD1 (CCS), but a CCS-independent alternative pathway also exists and functions under anaerobic conditions. To explore the possible involvement of DJ-1 in such a pathway in vivo, we exposed to anoxia and evaluated the effect of DJ-1 on fly survival and SOD1 levels, in the presence or absence of CCS. Loss of DJ-1 negatively affects the fly response to the anoxic treatment, but our data indicate that the protective activity of DJ-1 is independent of SOD1 in , indicating that the two proteins may act in different pathways.
氧化还原稳态是一个至关重要的过程，其维持由众多抗氧化小分子和酶来保证，而其改变则涉及许多病理状况，包括几种神经退行性疾病。在参与抗氧化反应的不同酶中，超氧化物歧化酶1（SOD1）和DJ-1都与肌萎缩侧索硬化症和帕金森病的发病机制有关，这表明它们在作用机制上可能存在相互作用。有人提出，SOD1活性位点的铜缺乏是SOD1相关神经退行性变的核心决定因素。SOD1的成熟主要依赖于SOD1的蛋白质铜伴侣（CCS）的存在，但也存在一条不依赖CCS的替代途径，且在无氧条件下起作用。为了探究DJ-1在体内是否可能参与这样一条途径，我们使果蝇暴露于缺氧环境，并在有或没有CCS的情况下，评估DJ-1对果蝇存活和SOD1水平的影响。DJ-1的缺失对果蝇对缺氧处理的反应产生负面影响，但我们的数据表明，在果蝇中DJ-1的保护活性独立于SOD1，这表明这两种蛋白质可能在不同途径中发挥作用。
