Coenyzme Q4 is a functional substitute for coenyzme Q10 and can be targeted to the mitochondria
Steenberge, L. H.; Sung, A. Y.; Fan, J.; Pagliarini, D. J.
Show abstract
Coenzyme Q10 (CoQ10) is an important cofactor and antioxidant for numerous cellular processes, and its deficiency has been linked to human disorders including mitochondrial disease, heart failure, Parkinsons disease, and hypertension. Unfortunately, treatment with exogenous oral CoQ10 is often ineffective, likely due to the extreme hydrophobicity and high molecular weight of CoQ10. Here, we show that less hydrophobic CoQ species with shorter isoprenoid tails can serve as viable substitutes for CoQ10 in human cells. We demonstrate that CoQ4 can perform multiple functions of CoQ10 in CoQ-deficient cells at markedly lower treatment concentrations, motivating further investigation of CoQ4 as a supplement for CoQ10 deficiencies. In addition, we describe the synthesis and evaluation of an initial set of compounds designed to target CoQ4 selectively to mitochondria using triphenylphosphonium (TPP). Our results indicate that select versions of these compounds can successfully be delivered to mitochondria in a cell model and be cleaved to produce CoQ4, laying the groundwork for further development.
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