Characterization of cellular uptake and distribution of coenzyme Q 10 and vitamin E in PC12 cells ☆ Yoshiro Saito a,c, ⁎ , Akiko Fukuhara a , Keiko Nishio a , Mieko Hayakawa a , Yoko Ogawa a , Hirokazu Sakamoto b , Kenji Fujii b , Yasukazu Yoshida a , Etsuo Niki a a Human Stress Signal Research Center (HSSRC), National Institute of Advanced Industrial Science and Technology (AIST), Ikeda, Osaka 563-8577, Japan b Functional Food Ingredients Division, Kaneka Corporation, Japan c Department of Medical Life Systems, Faculty of Medical and Life Sciences, Doshisha University, Kyotanabe, Kyoto 610-0321, Japan Received 8 January 2008; received in revised form 15 March 2008; accepted 14 April 2008 Abstract Coenzyme Q (CoQ) is a well-known electron transporter in the mitochondrial respiratory chain. Furthermore, ubiquinol (UQH 2 ) — a reduced form of ubiquinone (UQ) — has been shown to act as a radical-scavenging antioxidant. Some studies have reported the beneficial effect of CoQ addition to cultured cells; however, the cellular uptake and distribution of CoQ have not been elucidated. In the present study, we used rat pheochromocytoma PC12 cells to investigate and compare the cellular uptake and distribution of CoQ 10 and α-tocopherol (αT). UQ 10 or UQ 10 H 2 treatment resulted in an increase in the cellular content of both CoQ 10 in a time- and concentration-dependent manner. A subcellular fractionation study revealed that the added UQ 10 as well as UQ 10 H 2 mainly localized in the mitochondrial fraction, which is similar to the localization of endogenous CoQ but different from that of αT. The cellular distribution of αT directly corresponded to the lipid distribution, while the CoQ distribution did not show any relationship with the lipid distribution, particularly in the mitochondrial and microsomal fractions. These results indicate that the cellular distribution of CoQ is completely different from that of αT; moreover, a certain system which accumulates CoQ preferentially in mitochondria may be suggested. © 2009 Elsevier Inc. All rights reserved. Keywords: Coenzyme Q; Vitamin E; Cellular uptake; Cellular distribution; Subcellular fractionation study 1. Introduction The involvement of lipid peroxidation in in vivo oxidative damage and in the pathogenesis of several disorders and diseases induced by reactive oxygen and nitrogen species is widely accepted. Lipid peroxidation may directly damage biological molecules and membranes and may also induce the generation of toxic and signaling molecules [1–3]. Based on this, the potential role of antioxidant nutrients has been investigated in relation to the prevention of cancer, cardiovascular disease, cataract, age-related macular degen- eration and aging. Coenzyme Q (CoQ) is a well-known electron transporter in complexes of the mitochondrial respiratory chain [4]. It has been known that in CoQ, there are two forms, namely, oxidized form (ubiquinone, UQ) and reduced form (ubiqui- nol, UQH 2 ). Redox functions of CoQ are due to its ability to exchange two electrons in a redox cycle between UQ and UQH 2 . CoQ is synthesized in vivo and performs several functions that are of great importance with regard to cellular metabolism, including ATP synthesis. Furthermore, it has also been shown that UQH 2 , a reduced form of UQ, acts as a radical-scavenging antioxidant [5,6]. For example, UQH 2 can prevent lipid peroxidation in most subcellular mem- branes [5]; it functions as a reducing agent against α- tocopheroxyl radicals in liposomal suspensions [6] and in low-density lipoprotein [7]. Based on the total hydroxyocta- decadienoic acid (tHODE) levels and stereoisometric ratio, Available online at www.sciencedirect.com Journal of Nutritional Biochemistry 20 (2009) 350 – 357 ☆ This study was supported by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (18790081 and 19300256). ⁎ Corresponding author. Department of Medical Life Systems, Faculty of Medical and Life Sciences, Doshisha University, Kyotanabe, Kyoto 610- 0321, Japan. Tel.: +81 774 65 6258; fax: +81 774 65 6258. E-mail address: ysaito@mail.doshisha.ac.jp (Y. Saito). 0955-2863/$ – see front matter © 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.jnutbio.2008.04.005