{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T03:51:15Z","timestamp":1791517875782,"version":"4.3.4"},"reference-count":141,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Lactate is no longer viewed simply as a glycolytic end\u2010product, but as a compartmentalized signaling metabolite that coordinates energy production, carbon redistribution, redox balance, and anabolic commitment. This review discusses lactate as a regulator of the catabolism\u2010anabolism axis, emphasizing two major patterns of molecular interpretation. First, lactate acts through non\u2010covalent mechanisms, including transporter\u2010mediated flux, receptor\u2010dependent sensing, pH\u2010linked effects, and direct binding to intracellular proteins. These processes allow lactate\u2010rich states to rapidly couple metabolic flux to signaling pathways. Second, lactate\u2010associated metabolic states are translated into the dynamic and reversible change of covalent post\u2010translational modifications, including histone and non\u2010histone lactylation. Histone lactylation connects glycolytic metabolism to transcriptional regulation, whereas non\u2010histone lactylation expands lactate\u2010dependent control to immune signaling, mitochondrial metabolism, DNA repair, cardiovascular stress, tissue remodeling, and cancer progression. We further discuss how extracellular, cytosolic, mitochondrial\u2010associated, and nuclear lactate pools provide distinct biochemical contexts in which lactate\u2010dependent mechanisms can operate. By integrating lactate transport, receptor sensing, protein binding, metabolism, and lactylation, this Review uses compartmental organization as a framework for synthesizing how lactate\u2010rich states influence metabolic adaptation, stress responses, immune regulation, tissue remodeling, disease progression, and, in selected contexts, anabolic or reparative programs.<\/jats:p>","DOI":"10.1002\/advs.78115","type":"journal-article","created":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T03:35:41Z","timestamp":1791516941000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Lactate Signal: Modulator of Cellular Energy Production and Anabolism"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1442-4539","authenticated-orcid":false,"given":"Han","family":"Wang","sequence":"first","affiliation":[{"name":"The Obstetrics &amp; Gynecology Hospital of Fudan University Shanghai Key Lab of Reproduction and Development Shanghai Key Lab of Female Reproductive Endocrine Related Diseases Shanghai Key Laboratory of Metabolic Remodeling and Health Institute of Metabolism and Integrative Biology and State Key Laboratory of Genetics and Development of Complex Phenotypes Fudan University  Shanghai People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si\u2010Yuan","family":"Yang","sequence":"additional","affiliation":[{"name":"The Obstetrics &amp; Gynecology Hospital of Fudan University Shanghai Key Lab of Reproduction and Development Shanghai Key Lab of Female Reproductive Endocrine Related Diseases Shanghai Key Laboratory of Metabolic Remodeling and Health Institute of Metabolism and Integrative Biology and State Key Laboratory of Genetics and Development of Complex Phenotypes Fudan University  Shanghai People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9858-589X","authenticated-orcid":false,"given":"Wei","family":"Xu","sequence":"additional","affiliation":[{"name":"The Obstetrics &amp; Gynecology Hospital of Fudan University Shanghai Key Lab of Reproduction and Development Shanghai Key Lab of Female Reproductive Endocrine Related Diseases Shanghai Key Laboratory of Metabolic Remodeling and Health Institute of Metabolism and Integrative Biology and State Key Laboratory of Genetics and Development of Complex Phenotypes Fudan University  Shanghai People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,8]]},"reference":[{"issue":"3191","key":"e_1_2_11_2_1","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1126\/science.123.3191.309","article-title":"On the Origin of Cancer Cells","volume":"123","author":"Warburg O.","year":"1956","journal-title":"Science"},{"issue":"4","key":"e_1_2_11_3_1","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1016\/j.cmet.2018.03.008","article-title":"The Science and Translation of Lactate Shuttle Theory","volume":"27","author":"Brooks G. 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