Cholesterol biosynthetic stress limits coenzyme Q export from mitochondria

\The regulation of distribution of intracellular Coenzyme Q (CoQ), a hydrophobic lipid CoQ is not understood although it is synthesized in the mitochondria and present  in non-mitochondrial membranes .

The researchers in this study identify a key role for the mevalonate pathway in regulating CoQ distribution. The mevalonate pathway synthesizes isopentenyl pyrophosphate (IPP) as the precursor metabolite for both CoQ and cholesterol. The authors demonstrate that CoQ synthesis remains stable regardless of whether the mevalonate pathway is upregulated or downregulated.

However, upregulation of HMG-CoA reductase (HMGCR), indicative of increased mevalonate flux, enhances cholesterol ester synthesis without altering CoQ levels. When the pathway is downregulated, cholesterol synthesis declines, yet mitochondrial CoQ levels are preserved.

Under these limiting conditions, mitochondria reduce CoQ export to maintain their internal CoQ pool. While this adaptation sustains mitochondrial respiration, it diminishes extramitochondrial CoQ availability and sensitizes cells to ferroptosis.

https://rupress.org/jcb/article/225/8/e202507174/282718/Mitochondria-limit-coenzyme-Q-export-under

https://sciencemission.com/Mitochondria-limit-coenzyme-Q-export