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Primary coenzyme Q 10 (CoQ 10 ) deficiency is unique among mitochondrial respiratory chain disorders in that it is potentially treatable if high-dose CoQ 10 supplements are given in the early stages of the disease. While supplements improve peripheral abnormalities, neurological symptoms are only partially or temporarily ameliorated. The reasons for this refractory response to CoQ 10 supplementation are unclear, however, a contributory factor may be the poor transfer of CoQ 10 across the blood-brain barrier (BBB). The aim of this study was to investigate mechanisms of CoQ 10 transport across the BBB, using normal and pathophysiological (CoQ 10 deficient) cell culture models. The study identifies lipoprotein-associated CoQ 10 transcytosis in both directions across the in vitro BBB. Uptake via SR-B1 (Scavenger Receptor) and RAGE (Receptor for Advanced Glycation Endproducts), is matched by efflux via LDLR (Low Density Lipoprotein Receptor) transporters, resulting in no "net" transport across the BBB. In the CoQ 10 deficient model, BBB tight junctions were disrupted and CoQ 10 "net" transport to the brain side increased. The addition of anti-oxidants did not improve CoQ 10 uptake to the brain side. This study is the first to generate in vitro BBB endothelial cell models of CoQ 10 deficiency, and the first to identify lipoprotein-associated uptake and efflux mechanisms regulating CoQ 10 distribution across the BBB. The results imply that the uptake of exogenous CoQ 10 into the brain might be improved by the administration of LDLR inhibitors, or by interventions to stimulate luminal activity of SR-B1 transporters.

CoQ10 Deficient Endothelial Cell Culture Model for the Investigation of CoQ10 Blood–Brain Barrier Transport