PDF(Pubmed)
Abstract：
Maintenance of the proteasome requires oxidative phosphorylation (ATP) and mitigation of oxidative damage, in an increasingly dysfunctional relationship with aging. SLC3A2 plays a role on both sides of this dichotomy as an adaptor to SLC7A5, a transporter of branched-chain amino acids (BCAA: Leu, Ile, Val), and to SLC7A11, a cystine importer supplying cysteine to the synthesis of the antioxidant glutathione. Endurance in mammalian muscle depends in part on oxidation of BCAA; however, elevated serum levels are associated with insulin resistance and shortened lifespans. Intriguingly, the evolution of modern birds (Neoaves) has entailed the purging of genes including SLC3A2, SLC7A5, -7, -8, -10, and SLC1A4, -5, largely removing BCAA exchangers and their interacting Na+/Gln symporters in pursuit of improved energetics. Additional gene purging included mitochondrial BCAA aminotransferase (BCAT2), pointing to reduced oxidation of BCAA and increased hepatic conversion to triglycerides and glucose. Fat deposits are anhydrous and highly reduced, maximizing the fuel/weight ratio for prolonged flight, but fat accumulation in muscle cells of aging humans contributes to inflammation and senescence. Duplications of the bidirectional α-ketoacid transporters SLC16A3, SLC16A7, the cystine transporters SLC7A9, SLC7A11, and N-glycan branching enzymes MGAT4B, MGAT4C in Neoaves suggests a shift to the transport of deaminated essential amino acid, and stronger mitigation of oxidative stress supported by the galectin lattice. We suggest that Alfred Lotka\'s theory of natural selection as a maximum power organizer (PNAS 8:151,1922) made an unusually large contribution to Neoave evolution. Further molecular analysis of Neoaves may reveal novel rewiring with applications for human health and longevity.
摘要：
蛋白酶体的维持需要氧化磷酸化（ATP）和减轻氧化损伤，与衰老的功能失调关系越来越大。SLC3A2在这种二分法的两侧都起着作用，作为SLC7A5的衔接子，SLC7A5是支链氨基酸的转运蛋白（BCAA：Leu，Ile,Val),和SLC7A11，一种为抗氧化剂谷胱甘肽的合成提供半胱氨酸的胱氨酸导入体。哺乳动物肌肉的耐力部分取决于BCAA的氧化，然而，血清水平升高与胰岛素抵抗和寿命缩短有关。有趣的是，现代鸟类（Neoaves）的进化需要清除包括SLC3A2，SLC7A5，-7，-8，-10和SLC1A4，-5在内的基因，从而在很大程度上消除了BCAA交换剂及其相互作用的Na/Gln共生蛋白，以追求改进的能量学。额外的基因清除包括线粒体BCAA转氨酶（BCAT2），指出BCAA的氧化减少，肝脏向甘油三酯和葡萄糖的转化增加。脂肪沉积物是无水的，高度还原，最大化延长飞行的燃料/重量比，但是衰老的人类肌肉细胞中的脂肪积累会导致炎症，和衰老。双向α-酮酸转运蛋白SLC16A3，SLC16A7，胱氨酸转运蛋白SLC7A9，SLC7A11和N-聚糖分支酶MGAT4B的重复，Neoaves中的MGAT4C表明向脱氨基必需氨基酸的运输转移，以及由半乳糖凝集素晶格支持的更强的氧化应激缓解。我们建议AlfredLotka的自然选择理论作为最大功率组织者（PNAS8：151,1922）对Neoave进化做出了异常大的贡献。对Neoaves的进一步分子分析可能揭示了对人类健康和长寿应用的新颖重新布线。
