Dataset Information

Mitochondrial ATP generation is more proteome efficient than glycolysis (I. orientalis)

ABSTRACT: Metabolic efficiency profoundly influences organismal fitness. Heterotrophs, from yeast to mammals, derive usable energy primarily through glycolysis and respiration. While 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 (i.e. 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 yeasts, 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 is valuable for hypoxic growth. Aerobic glycolytic yeasts do not excel at aerobic growth, but outgrow respiratory cells in oxygen limitation. Thus, aerobic glycolysis emerges from cells maintaining a proteome conducive to both aerobic and hypoxic growth.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Pichia Kudriavzevii

TISSUE(S): Cell Suspension Culture, Cell Line Cell

DISEASE(S): Disease Free

SUBMITTER: Edward Cruz

LAB HEAD: Martin Wuhr

PROVIDER: PXD048012 | Pride | 2024-04-25

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	TGR_09417_w_TMT.mzIdentML	Mzid
	TGR_09417_w_TMT.raw	Raw
	TGR_11412_IO_noTMT_w_UPS2-Spike.mzIdentML	Mzid
	TGR_11412_IO_noTMT_w_UPS2-Spike.raw	Raw
	TGR_11413_IO_noTMT_w_UPS2-Spike.mzIdentML	Mzid

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Publications

Mitochondrial ATP generation is more proteome efficient than glycolysis.

Shen Yihui Y Dinh Hoang V HV Cruz Edward R ER Chen Zihong Z Bartman Caroline R CR Xiao Tianxia T Call Catherine M CM Ryseck Rolf-Peter RP Pratas Jimmy J Weilandt Daniel D Baron Heide H Subramanian Arjuna A Fatma Zia Z Wu Zong-Yen ZY Dwaraknath Sudharsan S Hendry John I JI Tran Vinh G VG Yang Lifeng L Yoshikuni Yasuo Y Zhao Huimin H Maranas Costas D CD Wühr Martin M Rabinowitz Joshua D JD

Nature chemical biology 20240306 9

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 proteo ...[more]

PMID: 38448734

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Project description:In some of the earliest uses of genome-wide gene-expression microarrays and array-based Comparative Genomic Hybridization (aCGH), a set of diploid yeasts that had undergone experimental evolution under aerobic glucose limitation was used to explore how gene expression and genome structure had responded to this selection pressure. To more deeply understand how adaptation to one environment might constrain or enhance performance in another we have now identified the adaptive mutations in this set of clones using whole-genome sequencing, and have assessed whether the evolved clones had become generalists or specialists by assaying their fitness under three contrasting growth environments: aerobic and anaerobic glucose limitation and aerobic acetate limitation. Additionally, evolved clones and their common ancestor were assayed for gene expression, biomass estimates and residual substrate levels under the alternative growth conditions. Relative fitnesses were evaluated by competing each clone against a common reference strain in each environment. Unexpectedly, we found that the evolved clones also outperformed their ancestor under strictly fermentative and strictly oxidative growth conditions. We conclude that yeasts evolving under aerobic glucose limitation become generalists for carbon limitation, as the mutations selected for in one environment are advantageous in others. High-throughput sequencing of the evolved clones uncovered mutations in genes involved in glucose sensing, signaling, and transport that in part explain these physiological phenotypes, with different sets of mutations found in independently-evolved clones. Earlier gene expression data from aerobic glucose-limited cultures had revealed a shift from fermentation towards respiration in all evolved clones explaining increased fitness in that condition. However, because the evolved clones also show higher fitness under strictly anaerobic conditions and under conditions requiring strictly respirative growth, this switch cannot be the sole source of adaptive benefit. Furthermore, because independently evolved clones are genetically distinct we conclude that there are multiple mutational paths leading to the generalist phenotype. Strain Name: Parental strain (CP1AB) or evolved clones (E1 - E5) Media: aerobic / anaerobic 36 hybridizations