Barrera Giuseppina, Gentile Fabrizio, Pizzimenti Stefania, Canuto Rosa Angela, Daga Martina, Arcaro Alessia, Cetrangolo Giovanni Paolo, Lepore Alessio, Ferretti Carlo, Dianzani Chiara, Muzio Giuliana
Dipartimento di Scienze Cliniche e Biologiche, Università di Torino, Torino 10125, Italy.
Dipartimento di Medicina e Scienze della Salute "V. Tiberio", Università del Molise, Campobasso 86100, Italy.
Antioxidants (Basel). 2016 Feb 19;5(1):7. doi: 10.3390/antiox5010007.
In several human diseases, such as cancer and neurodegenerative diseases, the levels of reactive oxygen species (ROS), produced mainly by mitochondrial oxidative phosphorylation, is increased. In cancer cells, the increase of ROS production has been associated with mtDNA mutations that, in turn, seem to be functional in the alterations of the bioenergetics and the biosynthetic state of cancer cells. Moreover, ROS overproduction can enhance the peroxidation of fatty acids in mitochondrial membranes. In particular, the peroxidation of mitochondrial phospholipid cardiolipin leads to the formation of reactive aldehydes, such as 4-hydroxynonenal (HNE) and malondialdehyde (MDA), which are able to react with proteins and DNA. Covalent modifications of mitochondrial proteins by the products of lipid peroxidation (LPO) in the course of oxidative cell stress are involved in the mitochondrial dysfunctions observed in cancer and neurodegenerative diseases. Such modifications appear to affect negatively mitochondrial integrity and function, in particular energy metabolism, adenosine triphosphate (ATP) production, antioxidant defenses and stress responses. In neurodegenerative diseases, indirect confirmation for the pathogenetic relevance of LPO-dependent modifications of mitochondrial proteins comes from the disease phenotypes associated with their genetic alterations.
在几种人类疾病中，如癌症和神经退行性疾病，主要由线粒体氧化磷酸化产生的活性氧（ROS）水平会升高。在癌细胞中，ROS产生的增加与线粒体DNA（mtDNA）突变有关，而这些突变反过来似乎在癌细胞的生物能量学和生物合成状态的改变中发挥作用。此外，ROS的过度产生会增强线粒体膜中脂肪酸的过氧化作用。特别是，线粒体磷脂心磷脂的过氧化会导致反应性醛类的形成，如4-羟基壬烯醛（HNE）和丙二醛（MDA），它们能够与蛋白质和DNA发生反应。在氧化细胞应激过程中，脂质过氧化（LPO）产物对线粒体蛋白质的共价修饰与癌症和神经退行性疾病中观察到的线粒体功能障碍有关。这种修饰似乎会对线粒体的完整性和功能产生负面影响，特别是能量代谢、三磷酸腺苷（ATP）生成、抗氧化防御和应激反应。在神经退行性疾病中，线粒体蛋白质LPO依赖性修饰的致病相关性的间接证据来自与其基因改变相关的疾病表型。
