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An Apoptotic and Endosymbiotic Explanation of the Warburg and the Inverse Warburg Hypotheses

Otto Warburg, a Nobel prize winner, observed that cancer cells typically “switch” from aerobic to anaerobic respiration. He hypothesized that mitochondrial damage induces neoplastic transformation. In contrast, pathological aging is observed mainly in neuron cells in neurodegenerative diseases. Oxid...

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Autores principales: Kaczanowski, Szymon, Klim, Joanna, Zielenkiewicz, Urszula
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6213112/
https://www.ncbi.nlm.nih.gov/pubmed/30308966
http://dx.doi.org/10.3390/ijms19103100
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author Kaczanowski, Szymon
Klim, Joanna
Zielenkiewicz, Urszula
author_facet Kaczanowski, Szymon
Klim, Joanna
Zielenkiewicz, Urszula
author_sort Kaczanowski, Szymon
collection PubMed
description Otto Warburg, a Nobel prize winner, observed that cancer cells typically “switch” from aerobic to anaerobic respiration. He hypothesized that mitochondrial damage induces neoplastic transformation. In contrast, pathological aging is observed mainly in neuron cells in neurodegenerative diseases. Oxidative respiration is particularly active in neurons. There is inverse comorbidity between cancer and neurodegenerative diseases. This led to the creation of the “inverse Warburg hypothesis”, according to which excessive mitochondrial activity induces pathological aging. The findings of our studies suggest that both the Warburg effect and the “inverse Warburg hypothesis” can be elucidated by the activation or suppression of apoptosis through oxidative respiration. The key outcome of our phylogenetic studies was the discovery that apoptosis and apoptosis-like cell death evolved due to an evolutionary “arms race” conducted between “prey” protomitochondrion and “predator” primitive eukaryotes. The ancestral protomitochondrial machinery produces and releases toxic mitochondrial proteins. Extant apoptotic factors evolved from these toxins. Our experiments indicate that the mitochondrial machinery is directly involved in adaptation to aerobic conditions. Additionally, our hypothesis is supported by the fact that different apoptotic factors are directly involved in respiration.
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spelling pubmed-62131122018-11-14 An Apoptotic and Endosymbiotic Explanation of the Warburg and the Inverse Warburg Hypotheses Kaczanowski, Szymon Klim, Joanna Zielenkiewicz, Urszula Int J Mol Sci Review Otto Warburg, a Nobel prize winner, observed that cancer cells typically “switch” from aerobic to anaerobic respiration. He hypothesized that mitochondrial damage induces neoplastic transformation. In contrast, pathological aging is observed mainly in neuron cells in neurodegenerative diseases. Oxidative respiration is particularly active in neurons. There is inverse comorbidity between cancer and neurodegenerative diseases. This led to the creation of the “inverse Warburg hypothesis”, according to which excessive mitochondrial activity induces pathological aging. The findings of our studies suggest that both the Warburg effect and the “inverse Warburg hypothesis” can be elucidated by the activation or suppression of apoptosis through oxidative respiration. The key outcome of our phylogenetic studies was the discovery that apoptosis and apoptosis-like cell death evolved due to an evolutionary “arms race” conducted between “prey” protomitochondrion and “predator” primitive eukaryotes. The ancestral protomitochondrial machinery produces and releases toxic mitochondrial proteins. Extant apoptotic factors evolved from these toxins. Our experiments indicate that the mitochondrial machinery is directly involved in adaptation to aerobic conditions. Additionally, our hypothesis is supported by the fact that different apoptotic factors are directly involved in respiration. MDPI 2018-10-10 /pmc/articles/PMC6213112/ /pubmed/30308966 http://dx.doi.org/10.3390/ijms19103100 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Kaczanowski, Szymon
Klim, Joanna
Zielenkiewicz, Urszula
An Apoptotic and Endosymbiotic Explanation of the Warburg and the Inverse Warburg Hypotheses
title An Apoptotic and Endosymbiotic Explanation of the Warburg and the Inverse Warburg Hypotheses
title_full An Apoptotic and Endosymbiotic Explanation of the Warburg and the Inverse Warburg Hypotheses
title_fullStr An Apoptotic and Endosymbiotic Explanation of the Warburg and the Inverse Warburg Hypotheses
title_full_unstemmed An Apoptotic and Endosymbiotic Explanation of the Warburg and the Inverse Warburg Hypotheses
title_short An Apoptotic and Endosymbiotic Explanation of the Warburg and the Inverse Warburg Hypotheses
title_sort apoptotic and endosymbiotic explanation of the warburg and the inverse warburg hypotheses
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6213112/
https://www.ncbi.nlm.nih.gov/pubmed/30308966
http://dx.doi.org/10.3390/ijms19103100
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