Reconstruction of the proto-mitochondrial metabolism
Reconstruction of the proto-mitochondrial metabolism
复制标题
DOI：
10.1126/science.1085463
复制
发表时间：
2003-08-01
期刊：
影响因子：
56.9
通讯作者：
Huynen, MA
中科院分区：
文献类型：
--
作者：
Gabaldón, T;Huynen, MA
两种新的假说解释了原噬菌体的α-变形菌祖先（1，2）与其宿主之间的最初关系，其中一种假说认为原噬菌体是氧清除剂（3），另一种假说认为它是一种产氢的兼性厌氧物种（4）。先前对原线粒体代谢的研究是基于α-变形菌来源的50种酵母线粒体蛋白（5）。为了检测α-变形菌来源的非线粒体蛋白质，我们比较了由6个α-变形菌基因组编码的蛋白质与包括9个真核生物在内的77个基因组，并推导出它们的同源性。在22525个重建的同源群中，630个同源群显示出α-变形菌和真核蛋白之间的密切进化关系，并且没有表明最近的水平转移（6）。我们认为这是对原线粒体蛋白质组的最小估计，因为它的许多基因可能已经从测序的真核生物基因组中丢失，或者没有足够强的系统发育信号在大规模分析中被检测到。这在Reclinomonasamericana的线粒体基因组中是明显的，我们的方法回收了61%的非核糖体蛋白（6）。对于许多途径[-氧化和完整的电子传递链;果糖/甘露糖代谢途径;以及脂质、生物素、血红素和铁硫簇的合成]，630组中回收的蛋白质的分数足够高，表明它们在原胞体中是完整的（图1）。柠檬酸循环（7）和戊糖磷酸途径只能部分恢复，而氨基酸和核苷酸代谢酶，虽然很好地代表，包含相对主要的“孤立的步骤”。丰富的代谢物转运蛋白表明宿主依赖的原线粒体。最重要的是发现了脂质转运蛋白和甘油摄取蛋白，它们分别与氧化和甘油代谢有关。相反，氨基酸和肽转运蛋白的存在与氨基酸代谢途径中的大量缺口一致。将原线粒体蛋白质组与来自酵母和人类的线粒体蛋白质的最大汇编进行比较（8）表明，线粒体蛋白质仅代表原线粒体血统的少数蛋白质（人类中为22%，酵母中为32%）。其余的，包括转运蛋白和代谢酶，已经被重新定位到细胞的其他部分，证实了（4）的预测。我们的结果证实了发现（5），即只有一小部分酵母线粒体蛋白质是α-变形菌来源的（16%），并将这一结果扩展到人类线粒体（14%）。重建的代谢表明一个好氧的原代谢酶分解代谢脂质，甘油和氨基酸提供的主机。尽管这与氧清除剂假说最相符，但在缺乏已发表的氢体真核生物基因组的情况下，这一结论无法确定。更重要的是，如果考虑到与三磷酸腺苷（ATP）生产没有直接关系的途径的保护，如果糖/甘露糖代谢和脂质、核苷酸和维生素的合成，那么内共生对宿主的多方面益处似乎是合理的。这些途径中的一些已经转移到细胞的其他地方，表明现代线粒体并不是α-变形杆菌与其宿主之间祖先共生关系的唯一遗产。
Two new hypotheses explain the initial relationship between the alpha-proteobacterial ancestor (1, 2) of the mitochondrion (the proto-mitochondrion) and its host, one in which the proto-mitochondrion would have been an oxygen scavenger (3) and the other in which it would have been a hydrogenproducing, facultatively anaerobic species (4). Previous studies on the proto-mitochondrion’s metabolism have been based on 50 yeast mitochondrial proteins of alpha-proteobacterial origin (5). To also detect nonmitochondrial proteins of alpha-proteobacterial origin, we compared the proteins encoded by six alphaproteobacterial genomes to a total of 77 genomes including nine eukaryotes, and derived their phylogenies. In the 22.525 reconstructed phylogenies, 630 orthologous groups showed a close evolutionary relationship between alphaproteobacterial and eukaryotic proteins and did not indicate more recent horizontal transfer (6). We consider this a minimal estimate of the proto-mitochondrial proteome, because many of its genes have likely been lost from the sequenced eukaryotic genomes or do not have a strong enough phylogenetic signal to be detected in large-scale analyses. This is apparent in the mitochondrial genome of Reclinomonas americana for which our method retrieved 61% of the nonribosomal proteins (6). For a number of pathways [-oxidation and a complete electron transport chain; fructose/mannose metabolism pathways; and for the synthesis of lipids, biotine, heme, and iron-sulfur clusters], the fraction of recovered proteins among the 630 groups is high enough to suggest they were complete in the proto-mitochondrion (Fig. 1). The citric acid cycle (7) and pentose phosphate pathway can only partially be recovered, whereas enzymes for amino acid and nucleotide metabolism, although well represented, contain relatively mainly “isolated steps.” The abundance of metabolite transporters suggests a host dependency of the protomitochondrion. Most significant are the finding of both a lipid transporter and a glycerol uptake protein, which can be linked tooxidation and glycerol metabolism, respectively. Conversely, the presence of amino acid and peptide transporters is consistent with the large number of gaps in pathways from the amino acid metabolism. Comparing the proto-mitochondrial proteome to the largest compilation of mitochondrial proteins from yeast and human (8) indicates that mitochondrial proteins represent only a minority of the proteins of protomitochondrial descent (22% in human and 32% in yeast). The rest, including transporters and metabolic enzymes, have been retargeted to other parts of the cell, corroborating a prediction from (4). Our results confirm findings (5) that only a minor fraction of yeast mitochondrial proteins are of alphaproteobacterial origin (16%) and extend this result to the human mitochondria (14%). The reconstructed metabolism suggests an aerobic proto-mitochondrion catabolizing lipids, glycerol, and amino acids provided by the host. Although this is most compatible with the oxygen-scavenger hypothesis, in the absence of a published genome of a hydrogenosomal eukaryote this conclusion cannot be definite. More important, a multifaceted benefit of the endosymbiosis for the host seems plausible if one considers the conservation of pathways not directly related to adenosine triphosphate (ATP) production, like fructose/mannose metabolism and the synthesis of lipids, nucleotides, and vitamins. Some of these pathways have moved elsewhere in the cell, showing that modern mitochondria are not the only heritage of the ancestral symbiotic relationship between an alphaproteobacterium and its host.