View source for Lu 2023 Explor Res Hypothesis Med

{{Publication
|title=Lu F (2023) Hypothetical hydrogenase activity of human mitochondrial Complex I and its role in preventing cancer transformation. Explor Res Hypothesis Med 8:280-5. https://doi.org/10.14218/ERHM.2022.00083
|info=[https://www.xiahepublishing.com/2472-0712/ERHM-2022-00083 Open Access]
|authors=Lu Fuxiong
|year=2023
|journal=Explor Res Hypothesis Med
|abstract=Cancer research has made a magnificent progress in past decades with an advancement of molecular biology. However, the mechanisms of cancer transformation are still not fully revealed. Thus, we must think about if there are some unknown factors playing a causative role in the cancer formation. Mitochondrial complex I oxidizes NADH to NAD+ and reduces ubiquinone to ubiquinol, regenerated NAD+ keeping pyruvate dehydrogenase and Krebs cycle function. Hydrogenases are widespread in nature, they occur in bacteria, archaea, and some eukarya. It is unknown whether hydrogenase activity exists in human mitochondria. The complex I shares a last common ancestor with hydrogenases, and is closely related with hydrogenase in sequence and modular structure. The hydrogenase activity has been observed recently in complex I of higher plants. Based on these observations, I propose a hypothesis that mitochondrial complex I in human may also retain the hydrogenase activity. The hypothetical hydrogenase activity could release excessive reducing equivalents of NADH from electron transport chain when a cell is in hypoxia, decreased oxidative phosphorylation or a low ATP demand. Loss of the hydrogenase activity may result in aerobic glycolysis, activation of pentose phosphate pathway, elevated lipid synthesis, and activations of oncoproteins via acetylation, all of these alterations lead to cell proliferations and cancer transformation. Reducing mitochondrial NADH/NAD+ ratio or recovering the hydrogenase activity would reverse the cell transformation.
|editor=Gnaiger E
}}
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{{Labeling
|diseases=Cancer
}}