{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T19:15:35Z","timestamp":1792178135184,"version":"4.4.0"},"reference-count":81,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2020,12,4]],"date-time":"2020-12-04T00:00:00Z","timestamp":1607040000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["NIH-NIDDK 5 P30 DK041301-30"],"award-info":[{"award-number":["NIH-NIDDK 5 P30 DK041301-30"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Tumors remodel their metabolism to support anabolic processes needed for replication, as well as to survive nutrient scarcity and oxidative stress imposed by their changing environment. In most healthy tissues, the shift from anabolism to catabolism results in decreased glycolysis and elevated fatty acid oxidation (FAO). This change in the nutrient selected for oxidation is regulated by the glucose-fatty acid cycle, also known as the Randle cycle. Briefly, this cycle consists of a decrease in glycolysis caused by increased mitochondrial FAO in muscle as a result of elevated extracellular fatty acid availability. Closing the cycle, increased glycolysis in response to elevated extracellular glucose availability causes a decrease in mitochondrial FAO. This competition between glycolysis and FAO and its relationship with anabolism and catabolism is conserved in some cancers. Accordingly, decreasing glycolysis to lactate, even by diverting pyruvate to mitochondria, can stop proliferation. Moreover, colorectal cancer cells can effectively shift to FAO to survive both glucose restriction and increases in oxidative stress at the expense of decreasing anabolism. However, a subset of B-cell lymphomas and other cancers require a concurrent increase in mitochondrial FAO and glycolysis to support anabolism and proliferation, thus escaping the competing nature of the Randle cycle. How mitochondria are remodeled in these FAO-dependent lymphomas to preferably oxidize fat, while concurrently sustaining high glycolysis and increasing de novo fatty acid synthesis is unclear. Here, we review studies focusing on the role of mitochondrial FAO and mitochondrial-driven lipid synthesis in cancer proliferation and survival, specifically in colorectal cancer and lymphomas. We conclude that a specific metabolic liability of these FAO-dependent cancers could be a unique remodeling of mitochondrial function that licenses elevated FAO concurrent to high glycolysis and fatty acid synthesis. In addition, blocking this mitochondrial remodeling could selectively stop growth of tumors that shifted to mitochondrial FAO to survive oxidative stress and nutrient scarcity.<\/jats:p>","DOI":"10.3390\/cells9122600","type":"journal-article","created":{"date-parts":[[2020,12,4]],"date-time":"2020-12-04T11:59:00Z","timestamp":1607083140000},"page":"2600","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":76,"title":["The Role of Mitochondrial Fat Oxidation in Cancer Cell Proliferation and Survival"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2124-8799","authenticated-orcid":false,"given":"Matheus Pinto","family":"De Oliveira","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Endocrinology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA"},{"name":"Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA"},{"name":"Molecular Biology Institute at UCLA, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5909-8570","authenticated-orcid":false,"given":"Marc","family":"Liesa","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Endocrinology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA"},{"name":"Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA"},{"name":"Molecular Biology Institute at UCLA, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1016\/S0140-6736(63)91500-9","article-title":"The glucose fatty-acid cycle its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus","volume":"281","author":"Randle","year":"1963","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1002\/(SICI)1099-0895(199812)14:4<263::AID-DMR233>3.0.CO;2-C","article-title":"Regulatory interactions between lipids and carbohydrates: The glucose fatty acid cycle after 35 years","volume":"14","author":"Randle","year":"1998","journal-title":"Diabetes Metab. 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