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

中文翻译：

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辅酶Q4是辅酶Q10的功能替代品，可以靶向线粒体


辅酶 Q10 (CoQ) 是许多细胞过程的重要辅助因子和抗氧化剂，其缺乏与线粒体疾病、心力衰竭、帕金森病和高血压等人类疾病有关。不幸的是，外源辅酶 Q 的治疗通常无效，可能是由于其极度疏水性和高分子量。在这里，我们证明具有较短类异戊二烯尾部的疏水性较低的 CoQ 物种可以作为人类细胞中 CoQ 的可行替代品。我们证明，CoQ 可以在明显较低的处理浓度下在 CoQ 缺陷细胞中发挥 CoQ 的多种功能，这激发了对 CoQ 作为 CoQ 缺陷补充的进一步研究。此外，我们描述了一组初始化合物的合成和评估，这些化合物旨在使用三苯基鏻选择性地将 CoQ 靶向线粒体。我们的结果表明，这些化合物的选定版本可以成功地递送至细胞模型中的线粒体，并被裂解产生 CoQ，为进一步开发奠定了基础。