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Warburg and Beyond: The Power of Mitochondrial Metabolism to Collaborate or Replace Fermentative Glycolysis in Cancer

1
Department of Medical Biology, Centre Scientifique de Monaco, CSM, 98000 Monaco, Monaco
2
Centre A. Lacassagne, University Côte d’Azur, IRCAN, CNRS, 06189 Nice, France
*
Authors to whom correspondence should be addressed.
Present address: Faculty of Medicine, University of Montenegro, Kruševac bb, 81000 Podgorica, Montenegro.
Cancers 2020, 12(5), 1119; https://doi.org/10.3390/cancers12051119
Received: 16 April 2020 / Revised: 27 April 2020 / Accepted: 29 April 2020 / Published: 30 April 2020
(This article belongs to the Special Issue Metabolic Pathways and Redox Homeostasis in Cancer)
A defining hallmark of tumor phenotypes is uncontrolled cell proliferation, while fermentative glycolysis has long been considered as one of the major metabolic pathways that allows energy production and provides intermediates for the anabolic growth of cancer cells. Although such a vision has been crucial for the development of clinical imaging modalities, it has become now evident that in contrast to prior beliefs, mitochondria play a key role in tumorigenesis. Recent findings demonstrated that a full genetic disruption of the Warburg effect of aggressive cancers does not suppress but instead reduces tumor growth. Tumor growth then relies exclusively on functional mitochondria. Besides having fundamental bioenergetic functions, mitochondrial metabolism indeed provides appropriate building blocks for tumor anabolism, controls redox balance, and coordinates cell death. Hence, mitochondria represent promising targets for the development of novel anti-cancer agents. Here, after revisiting the long-standing Warburg effect from a historic and dynamic perspective, we review the role of mitochondria in cancer with particular attention to the cancer cell-intrinsic/extrinsic mechanisms through which mitochondria influence all steps of tumorigenesis, and briefly discuss the therapeutic potential of targeting mitochondrial metabolism for cancer therapy. View Full-Text
Keywords: tumor; metabolism; Warburg effect; oxidative phosphorylation (OXPHOS); mitochondria; Krebs cycle; therapy tumor; metabolism; Warburg effect; oxidative phosphorylation (OXPHOS); mitochondria; Krebs cycle; therapy
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Cassim, S.; Vučetić, M.; Ždralević, M.; Pouyssegur, J. Warburg and Beyond: The Power of Mitochondrial Metabolism to Collaborate or Replace Fermentative Glycolysis in Cancer. Cancers 2020, 12, 1119.

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