Physical Biochemistry, Department of Chemistry, Technische Universität Darmstadt, Darmstadt, Germany.
Exp Gerontol. 2010 Aug;45(7-8):563-72. doi: 10.1016/j.exger.2010.02.003. Epub 2010 Feb 14.
Activity and stability of life-supporting proteins are determined not only by their abundance and by post-translational modifications, but also by specific protein-protein interactions. This holds true both for signal-transduction and energy-converting cascades. For vital processes such as life-span control and senescence, to date predominantly age-dependent alterations in abundance and to lesser extent in post-translational modifications of proteins are examined to elucidate the cause of ageing at the molecular level. In mitochondria of rat cortex, we quantified profound changes in the proportion of supramolecular assemblies (supercomplexes) of the respiratory chain complexes I, III(2), IV as well as of the MF(o)F(1) ATP synthase (complex V) by 2D-native/SDS electrophoresis and fluorescent staining. Complex I was present solely in supercomplexes and those lacking complex IV were least stable in aged animals (2.4-fold decline). The ATP synthase was confirmed as a prominent target of age-associated degradation by an overall decline in abundance of 1.5-fold for the monomer and an 2.8-fold increase of unbound F(1). Oligomerisation of the ATP synthase increases during ageing and might modulate the cristae architecture. These data could explain the link between ageing and respiratory control as well as ROS generation.
生命支持蛋白的活性和稳定性不仅取决于其丰度和翻译后修饰，还取决于特定的蛋白质-蛋白质相互作用。这对于信号转导和能量转换级联都是如此。对于生命过程，如寿命控制和衰老，迄今为止，主要研究了蛋白质丰度随年龄的依赖性改变，以及在翻译后修饰方面的较小程度改变，以阐明分子水平衰老的原因。在大鼠皮质的线粒体中，我们通过 2D-天然/SDS 电泳和荧光染色，定量分析了呼吸链复合物 I、III(2)、IV 以及 MF(o)F(1)ATP 合酶（复合物 V）的超分子组装（超级复合物）比例的深刻变化。复合物 I 仅存在于超级复合物中，而缺乏复合物 IV 的超级复合物在老年动物中最不稳定（下降 2.4 倍）。ATP 合酶作为与年龄相关的降解的主要靶标，通过单体丰度下降 1.5 倍和未结合的 F(1)增加 2.8 倍得到证实。ATP 合酶的寡聚化在衰老过程中增加，可能调节嵴的结构。这些数据可以解释衰老与呼吸控制以及 ROS 生成之间的联系。
