Echtay Karim S, Pakay Julian L, Esteves Telma C, Brand Martin D
Department of Biomedical Sciences, Faculty of Medicine and Medical Sciences, University of Balamand, Tripoli, Lebanon.
Biofactors. 2005;24(1-4):119-30. doi: 10.1002/biof.5520240114.
In this mini review we summarize recent studies from our laboratory that show the involvement of superoxide and the lipid peroxidation product 4-hydroxynonenal in the regulation of mitochondrial uncoupling. Superoxide produced during mitochondrial respiration is a major cause of the cellular oxidative damage that may underlie degenerative diseases and ageing. Superoxide production is very sensitive to the magnitude of the mitochondrial protonmotive force, so can be strongly decreased by mild uncoupling. Superoxide is able to give rise to other reactive oxygen species, which elicit deleterious effects primarily by oxidizing intracellular components, including lipids, DNA and proteins. Superoxide-induced lipid peroxidation leads to the production of reactive aldehydes, including 4-hydroxynonenal. These aldehydic lipid peroxidation products are in turn able to modify proteins such as mitochondrial uncoupling proteins and the adenine nucleotide translocase, converting them into active proton transporters. This activation induces mild uncoupling and so diminishes mitochondrial superoxide production, hence protecting against disease and oxidative damage at the expense of energy production.
在本综述中，我们总结了我们实验室最近的研究，这些研究表明超氧化物和脂质过氧化产物4-羟基壬烯醛参与线粒体解偶联的调节。线粒体呼吸过程中产生的超氧化物是细胞氧化损伤的主要原因，而细胞氧化损伤可能是退行性疾病和衰老的基础。超氧化物的产生对线粒体质子动力势的大小非常敏感，因此轻度解偶联可使其大幅降低。超氧化物能够产生其他活性氧，这些活性氧主要通过氧化细胞内成分（包括脂质、DNA和蛋白质）而引发有害作用。超氧化物诱导的脂质过氧化导致活性醛的产生，包括4-羟基壬烯醛。这些醛类脂质过氧化产物进而能够修饰蛋白质，如线粒体解偶联蛋白和腺嘌呤核苷酸转位酶，将它们转化为活性质子转运体。这种激活诱导轻度解偶联，从而减少线粒体超氧化物的产生，因此以能量产生为代价预防疾病和氧化损伤。
