Metabolic flux and flux balance analyses indicate the relevance of metabolic thermogenesis and aerobic glycolysis in cancer cells

Okahashi, Nobuyuki; Shima, Tomoki; Kondo, Yuya; Araki, Chie; Tsuji, Shuma; Sawai, Akane; Uehara, Hikaru; Kohno, Susumu; Shimizu, Hiroshi; Takahashi, Chiaki; Matsuda, Fumio

doi:https://doi.org/10.1016/j.ymben.2025.08.002

Metabolic flux and flux balance analyses indicate the relevance of metabolic thermogenesis and aerobic glycolysis in cancer cells

Okahashi, Nobuyuki; Shima, Tomoki; Kondo, Yuya et al.

Metabolic Engineering, 2025, 92, 185-193

アクセス数:19件（2025-12-02 14:33 集計）

固定URL: https://hdl.handle.net/11094/102861

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タイトル	Metabolic flux and flux balance analyses indicate the relevance of metabolic thermogenesis and aerobic glycolysis in cancer cells
著者	NRID 1000030802748 1000030802748 ORCID 0000-0001-9582-355X 0000-0001-9582-355X researchmap permalink okahashinobuyuki okahashinobuyuki Scopus Author ID 56549714700 56549714700 著者名 Okahashi, Nobuyuki
	著者名 Shima, Tomoki
	著者名 Kondo, Yuya
	著者名 Araki, Chie
	著者名 Tsuji, Shuma
	著者名 Sawai, Akane
	著者名 Uehara, Hikaru
	NRID 1000030625463 1000030625463 著者名 Kohno, Susumu
	NRID 1000000226250 1000000226250 ORCID 0000-0002-8986-0861 0000-0002-8986-0861 researchmap permalink hiroshi_shimizu hiroshi_shimizu Scopus Author ID 55230249300 55230249300 著者名 Shimizu, Hiroshi
	NRID 1000050283619 1000050283619 著者名 Takahashi, Chiaki
	NRID 1000050462734 1000050462734 ORCID 0000-0003-1091-778X 0000-0003-1091-778X researchmap permalink fumio_matsuda fumio_matsuda Scopus Author ID 7202165617 7202165617 著者名 Matsuda, Fumio
キーワード等	Aerobic glycolysis
	Caner metabolism
	Flux balance analysis
	Metabolic flux analysis
	Metabolic heat
内容	Okahashi N., Shima T., Kondo Y., et al. Metabolic flux and flux balance analyses indicate the relevance of metabolic thermogenesis and aerobic glycolysis in cancer cells. Metabolic Engineering 92, 185 (2025); https://doi.org/10.1016/j.ymben.2025.08.002.
抄録	Adenosine triphosphate (ATP) regeneration by substrate-level phosphorylation is a general feature of cancer metabolism, even under normoxic conditions (aerobic glycolysis). However, it is unclear why cancer cells prefer inefficient aerobic glycolysis over the highly efficient process of oxidative phosphorylation for ATP regeneration. To investigate the metabolic principles underlying aerobic glycolysis, we performed 13C-metabolic flux analysis of 12 cultured cancer cell lines and explored the metabolic constraints required to reproduce the results using in silico metabolic simulations. We found that the measured flux distribution can be reproduced by maximizing the ATP consumption in the flux balance analysis considering a limitation of metabolic heat dissipation (enthalpy change). Consistent with the simulation, OXPHOS inhibition induced metabolic redirection to aerobic glycolysis while maintaining the intracellular temperature. Furthermore, the dependency on aerobic glycolysis was partly alleviated upon culturing at low temperatures. Our data suggest that metabolic thermogenesis is an important factor in understanding aerobic glycolysis in cancer cells and that an advantage of aerobic glycolysis is the reduction in metabolic heat generation during ATP regeneration.
出版者	Academic Press Inc.
収録物名	Metabolic Engineering
巻(号)	92
ページ	185-193
刊行年月	2025-11-01
言語	英語
ハンドルURL	https://hdl.handle.net/11094/102861
PISSN	10967176
eISSN	10967184
関連情報 (isIdenticalTo)	DOI (出版社版) https://doi.org/10.1016/j.ymben.2025.08.002
アクセス権	open access
権利情報	This article is licensed under a Creative Commons Attribution 4.0 International License.
出版タイプ	Version of Record
カテゴリ	学術雑誌論文 Journal Article

資源タイプ	学術雑誌論文
ローカル資源タイプ	学術雑誌論文
DCMI資源タイプ	text
DCTERMS.bibliographicCitation	Metabolic Engineering. 2025, 92, p. 185-193
DC.title	Metabolic flux and flux balance analyses indicate the relevance of metabolic thermogenesis and aerobic glycolysis in cancer cells
DC.creator	Okahashi, Nobuyuki
	Shima, Tomoki
	Kondo, Yuya
	Araki, Chie
	Tsuji, Shuma
	Sawai, Akane
	Uehara, Hikaru
	Kohno, Susumu
	Shimizu, Hiroshi
	Takahashi, Chiaki
	Matsuda, Fumio
DC.publisher	Academic Press Inc.
DC.language' scheme='DCTERMS.RFC1766	英語
DC.type' scheme='DCTERMS.DCMIType	text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2025-11-01
DC.identifier	https://doi.org/10.1016/j.ymben.2025.08.002
DC.subject	Aerobic glycolysis
	Caner metabolism
	Flux balance analysis
	Metabolic flux analysis
	Metabolic heat
DC.description	Okahashi N., Shima T., Kondo Y., et al. Metabolic flux and flux balance analyses indicate the relevance of metabolic thermogenesis and aerobic glycolysis in cancer cells. Metabolic Engineering 92, 185 (2025); https://doi.org/10.1016/j.ymben.2025.08.002.
DCTERMS.abstract	Adenosine triphosphate (ATP) regeneration by substrate-level phosphorylation is a general feature of cancer metabolism, even under normoxic conditions (aerobic glycolysis). However, it is unclear why cancer cells prefer inefficient aerobic glycolysis over the highly efficient process of oxidative phosphorylation for ATP regeneration. To investigate the metabolic principles underlying aerobic glycolysis, we performed 13C-metabolic flux analysis of 12 cultured cancer cell lines and explored the metabolic constraints required to reproduce the results using in silico metabolic simulations. We found that the measured flux distribution can be reproduced by maximizing the ATP consumption in the flux balance analysis considering a limitation of metabolic heat dissipation (enthalpy change). Consistent with the simulation, OXPHOS inhibition induced metabolic redirection to aerobic glycolysis while maintaining the intracellular temperature. Furthermore, the dependency on aerobic glycolysis was partly alleviated upon culturing at low temperatures. Our data suggest that metabolic thermogenesis is an important factor in understanding aerobic glycolysis in cancer cells and that an advantage of aerobic glycolysis is the reduction in metabolic heat generation during ATP regeneration.
DC.rights	This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	102861
citation_title	Metabolic flux and flux balance analyses indicate the relevance of metabolic thermogenesis and aerobic glycolysis in cancer cells
citation_author	Okahashi, Nobuyuki
	Shima, Tomoki
	Kondo, Yuya
	Araki, Chie
	Tsuji, Shuma
	Sawai, Akane
	Uehara, Hikaru
	Kohno, Susumu
	Shimizu, Hiroshi
	Takahashi, Chiaki
	Matsuda, Fumio
citation_publisher	Academic Press Inc.
citation_language	英語
citation_date	2025-11-01
citation_journal_title	Metabolic Engineering
citation_volume	92
citation_firstpage	185
citation_lastpage	193
citation_doi	https://doi.org/10.1016/j.ymben.2025.08.002
citation_public_url	https://hdl.handle.net/11094/102861

Metabolic flux and flux balance analyses indicate the relevance of metabolic thermogenesis and aerobic glycolysis in cancer cells

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