The mitochondrial production of reactive oxygen species in relation to aging and pathology
The mitochondrial production of reactive oxygen species in relation to aging and pathology
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DOI：
10.1196/annals.1293.010
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发表时间：
2004-01-01
期刊：
影响因子：
--
通讯作者：
Lenaz, G
中科院分区：
文献类型：
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作者：
Genova, ML;Pich, MM;Lenaz, G
众所周知，线粒体是活性氧物种(ROS)的强大生产者，同时特别容易受到它们对脂质、蛋白质和DNA的作用而产生的氧化损伤。特别是，线粒体DNA的损伤会导致呼吸复合体中线粒体DNA编码的多肽发生改变，从而导致电子传递减少，导致ROS的进一步产生，从而建立氧化应激和能量下降的恶性循环。线粒体能量能力的这种不足被认为是衰老和与年龄相关的退行性疾病的原因。复合体I将是受ROS影响最大的酶，因为它包含mtDNA编码的13个亚基中的7个。因此，我们发现，大鼠脑和肝脏线粒体以及人类血小板中的复合体i活性受到年龄的显著影响。此外，由于其对有氧呼吸的速率控制，这种变化反映在整个氧化磷酸化系统中。我们还研究了线粒体复合体I在超氧化物产生中的作用，发现氧的单电子供体很可能是Fe-S簇合物N_2。短链辅酶Q(CoQ)类似物可能通过在牛心脏SMP和培养的HL60细胞中介导从N_2到O的电子转移来促进ROS的形成。然而，我们已经积累了大量证据表明还原辅酶Q(10)在几个细胞系统中的抗氧化作用，并证明了DT黄递酶和其他细胞内还原酶在掺入后减少外源辅酶Q(10)的重要性。
Mitochondria are known to be strong producers of reactive oxygen species (ROS) and, at the same time, particularly susceptible to the oxidative damage produced by their action on lipids, proteins, and DNA. In particular, damage to mtDNA induces alterations to the polypeptides encoded by mtDNA in the respiratory complexes, with consequent decrease of electron transfer, leading to further production of ROS and thus establishing a vicious circle of oxidative stress and energetic decline. This deficiency in mitochondrial energetic capacity is considered the cause of aging and age-related degenerative diseases. Complex I would be the enzyme most affected by ROS, since it contains seven of the 13 subunits encoded by mtDNA. Accordingly, we found that complex I activity is significantly affected by aging in rat brain and liver mitochondria as well as in human platelets. Moreover, due to its rate control over aerobic respiration, such alterations are reflected on the entire oxidative phosphorylation system We also investigated the role of mitochondrial complex I in superoxide production anti found that the one-electron donor to oxygen is most probably the Fe-S cluster N2. Short chain coenzyme Q (CoQ) analogues enhance ROS formation, presumably by mediating electron transfer from N2 to oxygen, both in bovine heart SMP and in cultured HL60 cells. Nevertheless, we have accumulated much evidence of the antioxidant role of reduced CoQ(10) in several cellular systems and demonstrated the importance of DT diaphorase and other internal cellular reductases to reduce exogenous CoQ(10) after incorporation.