ATP is the primary energy currency required by living organisms. Mitochondrial oxidative phosphorylation (OxPhos) produces most of the ATP in quiescent and differentiated cells. OxPhos interruption results in analogous bioenergetic adaptations across divergent evolutionary taxa, yet this adaptation is poorly recognized. Oxygen availability is a major determinant of the source of ATP generation across most eukaryotic cell types. Acute oxygen deprivation, mitochondrial dysfunction, high energy demand, or other metabolic cues can shift relative ATP production from OxPhos to high-throughput fermentation via substrate-level phosphorylations (SLPs). Glucose-derived lactate and glutamine-derived succinate are biomarkers of cytosolic and mitochondrial SLP, respectively. The extracellular accumulation of these metabolites is observed in a broad range of biological systems, including unicellular bacteria and yeast to more complex mammalian cells, including those of the immune system, retina, and muscle. Unsurprisingly, many cancer cells accumulate excess lactate and succinate due to chronic OxPhos insufficiency. This review links ostensibly unique cases of metabolic disruption to the accumulation of lactate and succinate as biomarkers of compensatory fermentative metabolism through cytosolic and mitochondrial SLP. Fundamental principles of cellular energy and environmental adaptation are reviewed that span a broad range of biological complexity.
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| Evidence ID | Analyze ID | Gene/Complex | Systematic Name/Complex Accession | Qualifier | Gene Ontology Term ID | Gene Ontology Term | Aspect | Annotation Extension | Evidence | Method | Source | Assigned On | Reference |
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| Evidence ID | Analyze ID | Gene | Gene Systematic Name | Phenotype | Experiment Type | Experiment Type Category | Mutant Information | Strain Background | Chemical | Details | Reference |
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| Evidence ID | Analyze ID | Gene | Gene Systematic Name | Disease Ontology Term | Disease Ontology Term ID | Qualifier | Evidence | Method | Source | Assigned On | Reference |
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| Evidence ID | Analyze ID | Regulator | Regulator Systematic Name | Target | Target Systematic Name | Direction | Regulation of | Happens During | Regulator Type | Direction | Regulation Of | Happens During | Method | Evidence | Strain Background | Reference |
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| Site | Modification | Modifier | Source | Reference |
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| Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Allele | Assay | Annotation | Action | Phenotype | SGA score | P-value | Source | Reference | Note |
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Increase the total number of rows showing on this page by using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small "i" buttons located within a cell for an annotation to view further details about experiment type and any other genes involved in the interaction.
| Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Assay | Annotation | Action | Modification | Source | Reference | Note |
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| Complement ID | Locus ID | Gene | Species | Gene ID | Strain background | Direction | Details | Source | Reference |
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| Evidence ID | Analyze ID | Dataset | Description | Keywords | Number of Conditions | Reference |
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