The Warburg hypothesis and the emergence of the mitochondrial metabolic theory of cancer

https://m2.mtmt.hu/ hun 2026-09-21 21:40 JournalArticle 36085027 VALIDATED true Funding Agency and Grant Number: Foundation for Metabolic Cancer Therapies; Elizabeth Ann Weathers Breast Cancer Research Fund; Broken Science Initiative, Children with Cancer UK; Corkin Family Foundation; Boston College Research Expense Fund Funding text: We thank the Foundation for Metabolic Cancer Therapies, The Elizabeth Ann Weathers Breast Cancer Research Fund., Dr. Joseph C. Maroon, Dr. Edward Miller, The Broken Science Initiative, Children with Cancer UK, The Corkin Family Foundation, and the Boston College Research Expense Fund for their support. 0 false 2026-09-01T10:01:11.307+0000 2026-01-27T11:44:22.827+0000 2025-04-10T11:24:12.400+0000 true 10000059 Kolev Kraszimir Nikolaev /api/author/10000059 Author Kolev Kraszimir Nikolaev (Orvosi biokémia) true 10000059 2026-05-18T02:42:24.667+0000 2025-12-21T00:48:55.573+0000 true 521 Szuper Admin /api/admin/521 Admin Szuper Admin (admin) true true false true 24 24 /api/publicationtype/24 PublicationType Folyóiratcikk 1 true 24 JournalArticle true 1134514 Survey paper true 24 24 /api/publicationtype/24 PublicationType Folyóiratcikk 1 true 24 JournalArticle /api/subtype/1134514 Összefoglaló cikk SubType Összefoglaló cikk (Folyóiratcikk) 102 true 1134514 true 1 /api/category/1 Category Tudományos true 1 Seyfried, Thomas N. The Warburg hypothesis and the emergence of the mitochondrial metabolic theory of cancer true true /api/journal/2293 REVIEWED JOURNAL OF BIOENERGETICS AND BIOMEMBRANES 0145-479X 1573-6881 true false 2293 false 2293 true 0145-479X 1573-6881 Journal FOREIGN 57 2-3 57 83 57 27 2025 Otto Warburg originally proposed that cancer arose from a two-step process. The first step involved a chronic insufficiency of mitochondrial oxidative phosphorylation (OxPhos), while the second step involved a protracted compensatory energy synthesis through lactic acid fermentation. His extensive findings showed that oxygen consumption was lower while lactate production was higher in cancerous tissues than in non-cancerous tissues. Warburg considered both oxygen consumption and extracellular lactate as accurate markers for ATP production through OxPhos and glycolysis, respectively. Warburg’s hypothesis was challenged from findings showing that oxygen consumption remained high in some cancer cells despite the elevated production of lactate suggesting that OxPhos was largely unimpaired. New information indicates that neither oxygen consumption nor lactate production are accurate surrogates for quantification of ATP production in cancer cells. Warburg also did not know that a significant amount of ATP could come from glutamine-driven mitochondrial substrate level phosphorylation in the glutaminolysis pathway with succinate produced as end product, thus confounding the linkage of oxygen consumption to the origin of ATP production within mitochondria. Moreover, new information shows that cytoplasmic lipid droplets and elevated aerobic lactic acid fermentation are both biomarkers for OxPhos insufficiency. Warburg’s original hypothesis can now be linked to a more complete understanding of how OxPhos insufficiency underlies dysregulated cancer cell growth. These findings can also address several questionable assumptions regarding the origin of cancer thus allowing the field to advance with more effective therapeutic strategies for a less toxic metabolic management and prevention of cancer. true true 2025 true true true false true false GOLD 2026-09-01 true https://doi.org/10.1007/s10863-025-10059-w 23 0 23 17 1 23 23 22 18 23 23 17 17 17 6 0 23 17 23 17 0 18 18 Folyóiratcikk Journal Article 24 22 Könyvrészlet Chapter in Book 25 0 Könyv Book 23 1 Egyéb konferenciaközlemény Conference paper 31 0 Egyéb konferenciakötet Conference proceedings 32 0 Oltalmi formák Protection forms 26 0 Disszertáció Thesis 28 0 Egyéb Miscellaneous 29 0 Alkotás Achievement 22 0 Kutatási adat Research data 33 0 Folyóiratcikk Journal Article 24 0 0 0 Könyvrészlet Chapter in Book 25 0 0 0 Könyv Book 23 0 0 0 Egyéb konferenciaközlemény Conference paper 31 0 0 0 Egyéb konferenciakötet Conference proceedings 32 0 0 0 Oltalmi formák Protection forms 26 0 0 0 Disszertáció Thesis 28 0 0 0 Egyéb Miscellaneous 29 0 0 0 Alkotás Achievement 22 0 0 0 Kutatási adat Research data 33 0 0 0 2025 0 11 8 11 8 2026 0 12 9 12 9 Q2 false false false false 2025-07-09T11:24:52.551+0000 Biokémiai Tanszék (SE / AOK / I / BMBI) 1 9 1 8 0 true Language 10002 /api/language/10002 Angol Angol English true 2 true PersonAuthorship 126137037 /api/authorship/126137037 Seyfried, Thomas N. ✉ 1 0.125 true false true Seyfried Thomas N. true false false AuthorshipType 1 /api/authorshiptype/1 Szerző 0 true 0 true false true PersonAuthorship 126137038 /api/authorship/126137038 Lee, Derek C. 2 0.125 false false false Lee Derek C. true false false AuthorshipType 1 /api/authorshiptype/1 Szerző 0 true 0 true false true PersonAuthorship 126137039 /api/authorship/126137039 Duraj, Tomas 3 0.125 false false false Duraj Tomas true false false AuthorshipType 1 /api/authorshiptype/1 Szerző 0 true 0 true false true PersonAuthorship 126137040 /api/authorship/126137040 Ta, Nathan L. 4 0.125 false false false Ta Nathan L. true false false AuthorshipType 1 /api/authorshiptype/1 Szerző 0 true 0 true false true PersonAuthorship 126137041 /api/authorship/126137041 Mukherjee, Purna 5 0.125 false false false Mukherjee Purna true false false AuthorshipType 1 /api/authorshiptype/1 Szerző 0 true 0 true false true PersonAuthorship 126137042 /api/authorship/126137042 Kiebish, Michael 6 0.125 false false false Kiebish Michael true false false AuthorshipType 1 /api/authorshiptype/1 Szerző 0 true 0 true false true PersonAuthorship 126137043 /api/authorship/126137043 Arismendi-Morillo, Gabriel 7 0.125 false false false Arismendi-Morillo Gabriel true false false AuthorshipType 1 /api/authorshiptype/1 Szerző 0 true 0 true false true PersonAuthorship 126137044 /api/authorship/126137044 Chinopoulos, Christos [Chinopoulos, Christos (Bioenergetika), szerző] Biokémiai Tanszék (SE / AOK / I / BMBI) 8 0.125 false true false Author 10016754 /api/author/10016754 Chinopoulos Christos 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(2025) JOURNAL OF BIOENERGETICS AND BIOMEMBRANES 0145-479X 1573-6881 57 2-3 57-83<div class="JournalArticle Publication long-list"> <div class="authors"> <img title="Forrásközlemény" style="float: left" src="/frontend/resources/grid/publication-core-icon.png"> <img title="Idézőközlemény" style="float: left" src="/frontend/resources/grid/publication-citation-icon.png"> <div class="autype autype0"> <span class="author-name" >Seyfried Thomas N. ✉ </span> ;    <span class="author-name" >Lee Derek C. </span> ;    <span class="author-name" >Duraj Tomas </span> ;    <span class="author-name" >Ta Nathan L. </span> ;    <span class="author-name" >Mukherjee Purna </span> ;    <span class="author-name" >Kiebish Michael </span> ;    <span class="author-name" >Arismendi-Morillo Gabriel </span> ;    <span class="author-name" mtid="10016754"><a href="/gui2/?type=authors&mode=browse&sel=10016754" target="_blank">Chinopoulos Christos (<span class="authorship-author-name">Chinopoulos Christos</span> <span class="authorAux-mtmt"> Bioenergetika</span>) </a> </span> <span class="author-affil"><span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Intézet">I</span>/<span title="Biokémiai és Molekuláris Biológiai Intézet">BMBI</span>/Biokémiai Tanszék</span> </div> </div> <div class="title"><a href="/gui2/?mode=browse&params=publication;36085027" target="_blank">The Warburg hypothesis and the emergence of the mitochondrial metabolic theory of cancer</a></div> <div> <span class="journal-title">JOURNAL OF BIOENERGETICS AND BIOMEMBRANES</span> <span class="journal-issn">(<a target="_blank" href="https://portal.issn.org/resource/ISSN/0145-479X">0145-479X</a> <a target="_blank" href="https://portal.issn.org/resource/ISSN/1573-6881">1573-6881</a>)</span>: <span class="journal-volume">57</span> <span class="journal-issue">2-3</span> <span class="page"> pp 57-83 </span> <span class="year">(2025)</span> </div> <div class="pub-footer"> <span class="language" xmlns="http://www.w3.org/1999/html">Nyelv: Angol | </span> <span class="identifiers"> <span class="id identifier oa_GOLD" title=" Gold "> <a style="color:blue" title="10.1007/s10863-025-10059-w" target="_blank" href="https://doi.org/10.1007/s10863-025-10059-w"> DOI </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="001461675100001" target="_blank" href="https://www.webofscience.com/wos/woscc/full-record/001461675100001"> WoS </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:black" title="105002446656" target="_blank" href="http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-105002446656"> Scopus </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="40199815" target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=40199815&dopt=Abstract"> PubMed </a> </span> <span class="id identifier oa_NONE" title=" Nincs "> <a style="color:blue" title="https://www.scopus.com/inward/record.uri?eid=2-s2.0-105002446656&doi=10.1007%2Fs10863-025-10059-w&partnerID=40&md5=6810335ea2ba99350a0ffe075f71db21" target="_blank" href="https://www.scopus.com/inward/record.uri?eid=2-s2.0-105002446656&doi=10.1007%2Fs10863-025-10059-w&partnerID=40&md5=6810335ea2ba99350a0ffe075f71db21"> Egyéb URL </a> </span> </span> <OnlyViewableByAuthor><div class="ratings"> <div class="journal-subject">Folyóirat szakterülete: Scopus - Physiology   SJR indikátor: Q2</div> <div class="journal-subject">Folyóirat szakterülete: Scopus - Cell Biology   SJR indikátor: Q3</div> </div></OnlyViewableByAuthor> <div class="publication-citation" style="margin-left: 0.5cm;"> <span title="Nyilvános idézőközlemények összesen, említések nélkül" class="citingPub-count">Nyilvános idéző összesen: 23</span> | Független: 17 | Függő: 6 | Nem jelölt: 0 | WoS jelölt: 22 | Scopus jelölt: 18 | WoS/Scopus jelölt: 23 | DOI jelölt: 23 </div> <div class="publication-citation"> <a target="_blank" href="/api/publication?cond=citations.related;eq;36085027&sort=publishedYear,desc&sort=title"> Idézett közlemények száma: 18 </a> </div> <div class="mtid"><span class="long-pub-mtid">Közlemény: 36085027</span> | <span class="status-data status-VALIDATED"> Egyeztetett </span> Forrás Idéző | <span class="type-subtype">Folyóiratcikk ( Összefoglaló cikk ) </span> | <span class="pub-category">Tudományos</span> | <span class="publication-sourceOfData">kézi felvitel</span> </div> <div class="lastModified">Utolsó módosítás: 2026.01.27. 12:44 Kajtár Virág Anna (SE_AOK_Biokemia_Admin5_KV, admin) </div> <pre class="comment" style="margin-top: 0; margin-bottom: 0;"><u>Megjegyzés</u>: Funding Agency and Grant Number: Foundation for Metabolic Cancer Therapies; Elizabeth Ann Weathers Breast Cancer Research Fund; Broken Science Initiative, Children with Cancer UK; Corkin Family Foundation; Boston College Research Expense Fund Funding text: We thank the Foundation for Metabolic Cancer Therapies, The Elizabeth Ann Weathers Breast Cancer Research Fund., Dr. Joseph C. M...</pre> </div></div>