Coenzyme Q ₄ is a functional substitute for coenzyme Q ₁₀ and can be targeted to the mitochondria

Coenzyme Q ₁₀ (CoQ ₁₀ ) 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 oral CoQ ₁₀ is often ineffective, likely due to the extreme hydrophobicity and high molecular weight of CoQ ₁₀ . Here, we show that less hydrophobic CoQ species with shorter isoprenoid tails can serve as viable substitutes for CoQ ₁₀ in human cells. We demonstrate that CoQ ₄ can perform multiple functions of CoQ ₁₀ in CoQ-deficient cells at markedly lower treatment concentrations, motivating further investigation of CoQ ₄ as a supplement for CoQ ₁₀ deficiencies. In addition, we describe the synthesis and evaluation of an initial set of compounds designed to target CoQ ₄ 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 CoQ ₄ , laying the groundwork for further development.