Metabolic efficiency profoundly influences organismal fitness. Nonphotosynthetic organisms, from yeast to mammals, derive usable energy primarily through glycolysis and respiration. Although respiration is more energy efficient, some cells favor glycolysis even when oxygen is available (aerobic glycolysis, Warburg effect). A leading explanation is that glycolysis is more efficient in terms of ATP production per unit mass of protein (that is, faster). Through quantitative flux analysis and proteomics, we find, however, that mitochondrial respiration is actually more proteome efficient than aerobic glycolysis. This is shown across yeast strains, T cells, cancer cells, and tissues and tumors in vivo. Instead of aerobic glycolysis being valuable for fast ATP production, it correlates with high glycolytic protein expression, which promotes hypoxic growth. Aerobic glycolytic yeasts do not excel at aerobic growth but outgrow respiratory cells during oxygen limitation. We accordingly propose that aerobic glycolysis emerges from cells maintaining a proteome conducive to both aerobic and hypoxic growth.

代谢效率深刻影响机体健康。非光合生物，从酵母到哺乳动物，主要通过糖酵解和呼吸获得可用能量。尽管呼吸作用的能量效率更高，但一些细胞即使在有氧气的情况下也有利于糖酵解（有氧糖酵解，瓦尔堡效应）。一个主要的解释是，就每单位质量蛋白质的 ATP 生成而言，糖酵解效率更高（即更快）。然而，通过定量通量分析和蛋白质组学，我们发现线粒体呼吸实际上比有氧糖酵解的蛋白质组效率更高。这在酵母菌株、T 细胞、癌细胞、体内组织和肿瘤中都有体现。有氧糖酵解对于快速产生 ATP 并不有价值，而是与高糖酵解蛋白表达相关，从而促进缺氧生长。需氧糖酵解酵母不擅长有氧生长，但在氧气限制期间生长超过呼吸细胞。因此，我们认为有氧糖酵解是由维持有利于有氧和缺氧生长的蛋白质组的细胞产生的。