title: Knockdown of the coenzyme Q synthesis gene Smed-dlp1 affects planarian regeneration and tissue homeostasis.
abstract: The freshwater planarian is a model organism used to study tissue regeneration that occupies an important position among multicellular organisms. Planarian genomic databases have led to the identification of genes that are required for regeneration, with implications for their roles in its underlying mechanism. Coenzyme Q (CoQ) is a fundamental lipophilic molecule that is synthesized and expressed in every cell of every organism. Furthermore, CoQ levels affect development, life span, disease and aging in nematodes and mice. Because CoQ can be ingested in food, it has been used in preventive nutrition. In this study, we investigated the role of CoQ in planarian regeneration. Planarians synthesize both CoQ9 and rhodoquinone 9 (RQ9). Knockdown of Smed-dlp1, a trans-prenyltransferase gene that encodes an enzyme that synthesizes the CoQ side chain, led to a decrease in CoQ9 and RQ9 levels. However, ATP levels did not consistently decrease in these animals. Knockdown animals exhibited tissue regression and curling. The number of mitotic cells decreased in Smed-dlp1 (RNAi) animals. These results suggested a failure in physiological cell turnover and stem cell function. Accordingly, regenerating planarians died from lysis or exhibited delayed regeneration. Interestingly, the observed phenotypes were partially rescued by ingesting food supplemented with α-tocopherol. Taken together, our results suggest that oxidative stress induced by reduced CoQ9 levels affects planarian regeneration and tissue homeostasis.
authors.affiliation: Graduate School of Bionics, Tokyo University of Technology, Hachioji-shi, Tokyo 192-0982, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Shiobara
authors.affiliation: Graduate School of Bionics, Tokyo University of Technology, Hachioji-shi, Tokyo 192-0982, Japan.
authors.forename: Chiaki
authors.initials: C
authors.lastname: Harada
authors.affiliation: Graduate School of Bionics, Tokyo University of Technology, Hachioji-shi, Tokyo 192-0982, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Shiota
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Agriculture and Life Science, Hirosaki University, Aomori 036-8561, Japan.
authors.forename: Kimitoshi
authors.initials: K
authors.lastname: Sakamoto
authors.affiliation: Department of Biomedical Chemistry, Graduate School of Medicine, University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Kita
authors.affiliation: Graduate School of Bionics, Tokyo University of Technology, Hachioji-shi, Tokyo 192-0982, Japan.
authors.forename: Saeko
authors.initials: S
authors.lastname: Tanaka
authors.affiliation: Graduate School of Bionics, Tokyo University of Technology, Hachioji-shi, Tokyo 192-0982, Japan.
authors.forename: Kenta
authors.initials: K
authors.lastname: Tabata
authors.affiliation: Graduate School of Bionics, Tokyo University of Technology, Hachioji-shi, Tokyo 192-0982, Japan.
authors.forename: Kiyoteru
authors.initials: K
authors.lastname: Sekie
authors.affiliation: Graduate School of Bionics, Tokyo University of Technology, Hachioji-shi, Tokyo 192-0982, Japan.
authors.forename: Yorihiro
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Graduate School of Bionics, Tokyo University of Technology, Hachioji-shi, Tokyo 192-0982, Japan. Electronic address: tsugiyama@stf.teu.ac.jp.
authors.forename: Tomoyasu
authors.initials: T
authors.lastname: Sugiyama
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D053898:Biosynthetic Pathways; D004122:Dimethylallyltranstransferase / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006706:Homeostasis; D008969:Molecular Sequence Data; D010932:Planarians; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D012038:Regeneration; D014451:Ubiquinone / Q000096:biosynthesis*; D024502:alpha-Tocopherol / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D034741:RNA, Small Interfering; D014451:Ubiquinone; D004122:Dimethylallyltranstransferase; D024502:alpha-Tocopherol
keywords: Coenzyme Q; Planarian; RNAi; Reactive oxygen species; Regeneration; Trans-prenyltransferase