TY - JOUR
T1 - Mitochondrial ATP generation is more proteome efficient than glycolysis
AU - Shen, Yihui
AU - Dinh, Hoang V.
AU - Cruz, Edward R.
AU - Chen, Zihong
AU - Bartman, Caroline R.
AU - Xiao, Tianxia
AU - Call, Catherine M.
AU - Ryseck, Rolf Peter
AU - Pratas, Jimmy
AU - Weilandt, Daniel
AU - Baron, Heide
AU - Subramanian, Arjuna
AU - Fatma, Zia
AU - Wu, Zong Yen
AU - Dwaraknath, Sudharsan
AU - Hendry, John I.
AU - Tran, Vinh G.
AU - Yang, Lifeng
AU - Yoshikuni, Yasuo
AU - Zhao, Huimin
AU - Maranas, Costas D.
AU - Wühr, Martin
AU - Rabinowitz, Joshua D.
N1 - Publisher Copyright:
© The Author(s), under exclusive licence to Springer Nature America, Inc. 2024.
PY - 2024/9
Y1 - 2024/9
N2 - 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. (Figure presented.)
AB - 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. (Figure presented.)
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U2 - 10.1038/s41589-024-01571-y
DO - 10.1038/s41589-024-01571-y
M3 - Article
C2 - 38448734
AN - SCOPUS:85186887218
SN - 1552-4450
VL - 20
SP - 1123
EP - 1132
JO - Nature Chemical Biology
JF - Nature Chemical Biology
IS - 9
ER -