Palmitate-induced toxicity is associated with impaired mitochondrial respiration and accelerated oxidative stress in cultured cardiomyocytes: The critical role of coenzyme Q9/10

Impaired mitochondrial function concomitant to enhanced oxidative stress-induced damage are well established mechanisms involved in hyperlipidemia-induced cardiotoxicity. Currently, limited information is available on the direct effect of myocardial lipid overload on endogenous coenzyme Q9/10 (CoQ9/10) levels in association with mitochondrial respiration and oxidative stress status. Here, such effects were explored by exposing H9c2 cardiomyocytes to various doses (0.15 to 1 mM) of palmitate for 24 h. The results demonstrated that palmitate doses ≥0.25 mM are enough to impair mitochondrial respiration and cause oxidative stress. Although endogenous CoQ9/10 levels are enhanced by palmitate doses ≤0.5 mM, this is not enough to counteract oxidative stress, but is sufficient to maintain cell viability of cardiomyocytes. Palmitate doses >0.5 mM caused severe mitochondrial toxicity, including reduction of cell viability. Interestingly, enhancement of CoQ9/10 levels with the lowest dose of palmitate (0.15 mM) was accompanied by a significantly reduction of CoQ9 oxidation status, as well as low cytosolic production of reactive oxygen species. From the overall findings, it appears that CoQ9/10 response may be crucial to improve mitochondrial function in conditions linked to hyperlipidemia-induced insult. Confirmation of such findings in relevant in vivo models remains essential to better understand the cardioprotective effects in association with improving endogenous CoQ9/10 content.