01 December 2015 : Hypothesis
Cancer: Mitochondrial Origins
George B. StefanoEF, Richard M. KreamEFDOI: 10.12659/MSM.895990
Med Sci Monit 2015; 21:3736-3739
Abstract
The primacy of glucose derived from photosynthesis as an existential source of chemical energy across plant and animal phyla is universally accepted as a core principle in the biological sciences. In mammalian cells, initial processing of glucose to triose phosphate intermediates takes place within the cytosolic glycolytic pathway and terminates with temporal transport of reducing equivalents derived from pyruvate metabolism by membrane-associated respiratory complexes in the mitochondrial matrix. The intra-mitochondrial availability of molecular oxygen as the ultimate electron acceptor drives the evolutionary fashioned chemiosmotic production of ATP as a high-efficiency biological process. The mechanistic bases of carcinogenesis have demonstrated profound alteration of normative mitochondrial function, notably dysregulated respiratory processes. Accordingly, the classic Warburg effect functionally links aerobic glycolysis, aberrant production and release of lactate, and metabolic down-regulation of mitochondrial oxidative processes with the carcinogenetic phenotype. We surmise, however, that aerobic fermentation by cancer cells may also represent a developmental re-emergence of an evolutionarily conserved early phenotype, which was “sidelined” with the emergence of mitochondrial oxidative phosphorylation as a primary mechanism for ATP production in normal cells. Regardless of state-dependent physiological status in mixed populations of cancer cells, it has been established that mitochondria are functionally linked to the initiation of cancer and its progression. Biochemical, molecular, and physiological differences in cancer cell mitochondria, notably mtDNA heteroplasmy and allele-specific expression of selected nuclear genes, may represent major focal points for novel targeting and elimination of cancer cells in metastatic disease afflicting human populations. To date, and despite considerable research efforts, the practical realization of advanced mitochondrial targeted therapies has not been forthcoming.
Keywords: DNA, Mitochondrial - metabolism, Adenosine Triphosphate - metabolism, Energy Metabolism, Glucose - metabolism, Glycolysis, Mitochondria - metabolism, Neoplasms - metabolism
Editorial
01 February 2025 : Editorial
Editorial: Current Approaches to Screening for Lung Cancer in Smokers and Non-SmokersDOI: 10.12659/MSM.948255
Med Sci Monit 2025; 31:e948255
In Press
Clinical Research
Predicting Cerebral Small Vessel Disease Burden Based on Thromboelastography in Patients with Acute Ischemi...Med Sci Monit In Press; DOI: 10.12659/MSM.946303
Clinical Research
Long-Term Outcomes of Implanon in Managing Adenomyosis: A 3-Year Prospective StudyMed Sci Monit In Press; DOI: 10.12659/MSM.945972
Laboratory Research
Linear Dimensional Accuracy in Maxillomandibular Records: A Comparative Study of Scannable and Transparent ...Med Sci Monit In Press; DOI: 10.12659/MSM.947265
Clinical Research
Efficacy of King's Combined Uterine Suture in Managing Placenta Accreta: A Retrospective AnalysisMed Sci Monit In Press; DOI: 10.12659/MSM.945826
Most Viewed Current Articles
17 Jan 2024 : Review article 6,969,932
Vaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron VariantDOI :10.12659/MSM.942799
Med Sci Monit 2024; 30:e942799
16 May 2023 : Clinical Research 701,896
Electrophysiological Testing for an Auditory Processing Disorder and Reading Performance in 54 School Stude...DOI :10.12659/MSM.940387
Med Sci Monit 2023; 29:e940387
01 Mar 2024 : Editorial 25,741
Editorial: First Regulatory Approvals for CRISPR-Cas9 Therapeutic Gene Editing for Sickle Cell Disease and ...DOI :10.12659/MSM.944204
Med Sci Monit 2024; 30:e944204
28 Jan 2024 : Review article 20,253
A Review of IgA Vasculitis (Henoch-Schönlein Purpura) Past, Present, and FutureDOI :10.12659/MSM.943912
Med Sci Monit 2024; 30:e943912