When hypoxia -real or imaginary (due to malfunction of the oxygen sensors) – is sensed, the organism protects itself by stimulating oxygen intake and the cell protects itself by conserving oxygen by inhibiting respiration and stimulating fermentation of sugar, which produces valuable energy but consumes no oxygen. So clearly there is an oxygen-consuming process more critical to life (short term survival) than mitochondrial respiration and it must be given priority when oxygen tension is low, and it will mistakenly be given priority when oxygen tension is normal, but is mis-measured as low.
Malfunction of the oxygen sensors may be another contributor to the development of degenerative metabolism. Deficiencies in any or all of the following may contribute to faulty oxygen readings: oxoglutarate, iron, vitamin C, and antioxidant network defenses (resulting in more free radicals than the remaining vitamin C can handle, resulting in a stable Fe3+ configuration in the proline hydroxylase 2). An occasional burst of free radical production and deficiencies in proline hydroxylase 2 and/or the von Hippel Lindau factor may inhibit or block the turnover of HIF-1, and thus promote degenerative metabolism even in the presence of sufficient oxygen.
These more essential oxygen-requiring reactions: if their rate of production of ROS is actually higher than mitochondrial respiratiion, at least in certain circumstances, would there not be a feed forward inhibition of mitochondrial respiration? Higher ROS will itself tend to inhibit respiration.
What happens when sugar is limiting? Do other substrate level phosphorylations take precedence?