Evolutionary Pathobiochemistry Group, University Medical Center of the Johannes Gutenberg University, Duesbergweg 6, Mainz, Germany.
Mech Ageing Dev. 2011 Apr;132(4):171-9. doi: 10.1016/j.mad.2011.03.002. Epub 2011 Mar 29.
Mitochondrially encoded proteins in long-lived animals exhibit a characteristic anomaly on the amino acid usage level: they abstain from the use of cysteine in a lifespan-dependent fashion. Here, we have further investigated this phenomenon by analyzing respiratory chain complex subunits individually. We find that complex I cysteine depletion is the almost exclusive carrier of the cysteine-lifespan correlation, whereas complex IV cysteine depletion is uniform in all aerobic animals, unrelated to longevity, but even more pronounced than complex I cysteine depletion in the longest-lived species. In nuclear encoded subunits of the respiratory chain, we find lifespan-independent cysteine depletion ranging from moderate in complex I to severe in complex V. However, a separate analysis of the transmembrane domains of these proteins unmasks an intramembrane pattern of cysteine usage that significantly correlates with longevity. Hence, cysteine usage in the respiratory chain seems to be governed by two independent molecular mechanisms acting on the protein level: a global trend of cysteine avoidance in all proteins, and a specific effect on transmembrane domain cysteines that reflects longevity. To account for these characteristic patterns, a thiyl radical-based molecular mechanism of intramembrane hydrophobic cross-linking is discussed.
它们以依赖寿命的方式避免使用半胱氨酸。在这里，我们通过单独分析呼吸链复合物亚基进一步研究了这一现象。我们发现，复合物 I 半胱氨酸耗竭几乎是半胱氨酸-寿命相关性的唯一载体，而复合物 IV 半胱氨酸耗竭在所有需氧动物中都是均匀的，与寿命无关，但在寿命最长的物种中比复合物 I 半胱氨酸耗竭更为明显。在呼吸链的核编码亚基中，我们发现寿命独立的半胱氨酸耗竭程度从复合物 I 的中度到复合物 V 的严重不等。然而，对这些蛋白质跨膜结构域的单独分析揭示了一种跨膜区域半胱氨酸使用的膜内模式，与寿命显著相关。因此，呼吸链中的半胱氨酸使用似乎受到两种独立的作用于蛋白质水平的分子机制的控制：所有蛋白质中避免半胱氨酸的总体趋势，以及对反映寿命的跨膜区域半胱氨酸的特定影响。为了解释这些特征性模式，讨论了一种基于硫自由基的膜内疏水性交联的分子机制。
