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bioRxiv · 10.64898/2026.06.10.731318

Statin-Induced Mitochondrial Coenzyme Q Deficiency Alters Mitochondrial Redox Homeostasis and Bioenergetic Function in Astrocytes

Wojcicki, K.·Galganski, L.·Budzinska, A.·Figura, G.·Pijanowski, W.·Jarmuszkiewicz, W.
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Abstract

Statins, widely used cholesterol-lowering drugs, inhibit the mevalonate pathway and reduce coenzyme Q (CoQ) biosynthesis, potentially impairing mitochondrial function. Because astrocytes are essential for maintaining brain redox homeostasis, statin-induced mitochondrial dysfunction in these cells may contribute to CNS pathology. We examined the effects of a six-day statin exposure on mitochondrial bioenergetics in rat astrocytes, focusing on mitochondrial CoQ (mtCoQ) deficiency. Treatment with 200 nM atorvastatin or simvastatin decreased the total mtCoQ pool (mtCoQ9 + mtCoQ10) by 30-35% and decreased the antioxidant pool mtCoQH2 by 40%, whereas the levels of mitochondrial antioxidant proteins, including superoxide dismutase 2 and uncoupling proteins, remained unchanged. Mitochondria of statin-treated astrocytes showed decreased respiratory activity, membrane potential, and ATP synthesis, and increased mtCoQ reduction leading to increased H2O2 production during the oxidation of complex I (CI) and CII substrates. Statin treatment also altered the organization of the respiratory chain, leading to a downregulation of the CI+CIII2+CIV and CIII2+CIV supercomplexes and decreased protein levels and activity of all respiratory chain complexes. Furthermore, a decrease in cytochrome a + a3 content was accompanied by a reduction in the maximum activity of CIV. CoQ10 supplementation elevated mtCoQ levels, restored respiratory function, and decreased H2O2 production in the mitochondria of statin-treated astrocytes. Prolonged statin exposure alters mtCoQ redox homeostasis and impairs mitochondrial bioenergetic function in astrocytes. CoQ10 supplementation attenuates these changes, supporting its potential role in protecting astrocyte mitochondria from statin-induced dysfunction.

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Wojcicki, K., Galganski, L., Budzinska, A., Figura, G., Pijanowski, W., Jarmuszkiewicz, W.. 2026-06-10. Statin-Induced Mitochondrial Coenzyme Q Deficiency Alters Mitochondrial Redox Homeostasis and Bioenergetic Function in Astrocytes. https://doi.org/10.64898/2026.06.10.731318

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