An in vitro characterization of the bioenergetic effects of a phytosome-based Coenzyme Q10 formulation as a potential treatment for Troyer Syndrome

Coenzyme Q10 (CoQ10) plays a dual role in transferring electrons in the mitochondrial transport chain and acting as a membrane antioxidant. Due to its hydrophobic nature, several formulations have been developed to enhance its cellular uptake. We elucidated the bioenergetic and antioxidant effects of a CoQ10 phytosome formulation, UBIQSOME® (UBQ®) through two different studies. We investigated the potential benefits of UBQ® in I407 and H9c2 cells starting from the evaluation of cellular and mitochondrial content of CoQ10 and its redox state after UBQ® incubation. Oxygen consumption, ATP content, and mitochondrial potential were studied in UBQ® treated cells. The impact of UBQ® on oxidative stress, membrane lipid peroxidation, and ferroptosis was also investigated, highlighting the connection between CoQ10 concentration and its antioxidant efficacy. Furthermore, we explored the cellular mechanism regulating UBQ® internalization, revealing that the cell lines shared a common uptake mechanism, albeit with varying efficiency. In the second study, we demonstrated the crucial role of Spartin protein in nuclear-encoded mitochondrial proteins. Pathogenic Spartin variants are linked to Troyer syndrome, characterized by spasticity, weakness, short stature, cognitive impairment, and severe mitochondrial dysfunction. The identification of Spartin biallelic missense variants in a young patient with developmental delays and muscle weakness prompted further investigations. Patient-derived fibroblasts exhibited altered mitochondrial networks, decreased respiration, increased reactive oxygen species, and disrupted calcium dynamics compared to control cells. A mitochondrial protein import impairment was observed in fibroblasts and another cell model with a Spartin loss-of-function mutation, leading to a reduction in crucial CoQ10 synthesis enzymes and a drop in CoQ content. UBQ® supplementation and wild-type SPART re-expression equally restored ATP cell levels suggesting UBQ® treatment as a therapeutic approach for patients with Spartin mutations. This two different works highlight the intricate relationship between CoQ10 formulations, cellular bioenergetics, and the potential therapeutic impact in Troyer syndrome.