9-cis retinoic acid induces retinoid X receptor localized to the mitochondria for mediation of mitochondrial transcription.
We previously reported that 9-cis retinoic acid (RA) treatment induced an increase in mitochondrial (mt)DNA transcription. In order to extend these results, we tested various concentrations of 9-cis RA were used to treat 143B cells. Cells with low membrane potential treated with 9-cis RA showed significantly lower amounts of RXRalpha in mitochondria. We also found lower RXRalpha levels in mtDNA-depleted cells. Treating cells with 9-cis RA significantly increased expression of ND1, ND6, and COX I RNA. However, 9-cis RA-treatment did not appear to induce any significant changes in mtDNA copy number or mitochondrial mass. This study represents that 9-cis RA increases mtDNA transcription but not mtDNA replication, and it suggests that the effects of 9-cis RA on mitochondria are mediated by RXR localization to mitochondria. In addition, this is the first report that 9-cis RA regulation of RXR mitochondrial translocation depends on mitochondrial membrane potential and ATP.
Lin
Yung-Wei
YW
Department of Urology, Taipei Medical University-Wan Fang Hospital, 111, Section 3, Hsing-Long Road, Taipei 116, Taiwan, ROC.
Lien
Li-Ming
LM
Department of Neurology, Shin Kong Wu Ho-Su Memorial Hospital, 95, Wen-Chang Road, Taipei 111, Taiwan, ROC.
Yeh
Tien-Shun
TS
Institute of Anatomy and Cell Biology, Yang-Ming University, 155, Section 2, Linong Street, Taipei 112, Taiwan, ROC.
Wu
Hsiao-Mei
HM
School of Nutrition and Health Sciences, Taipei Medical University, 250 Wu-Hsing Street, Taipei 110, Taiwan, ROC.
Liu
Yi-Li
YL
School of Nutrition and Health Sciences, Taipei Medical University, 250 Wu-Hsing Street, Taipei 110, Taiwan, ROC.
Hsieh
Rong-Hong
RH
School of Nutrition and Health Sciences, Taipei Medical University, 250 Wu-Hsing Street, Taipei 110, Taiwan, ROC. Electronic address: hsiehrh@tmu.edu.tw.
D000077556:Alitretinoin; D045744:Cell Line, Tumor; D051545:Cyclooxygenase 1 / Q000235:genetics; D004261:DNA Replication / Q000187:drug effects; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism; D006801:Humans; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D009245:NADH Dehydrogenase / Q000235:genetics; D021381:Protein Transport / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis; D047490:Retinoid X Receptor alpha / Q000819:agonists* / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014212:Tretinoin / Q000494:pharmacology*
D004272:DNA, Mitochondrial; D012333:RNA, Messenger; D047490:Retinoid X Receptor alpha; D000077556:Alitretinoin; D014212:Tretinoin; D051545:Cyclooxygenase 1; C507225:MT-ND6 protein, human; D009245:NADH Dehydrogenase; C515075:NADH dehydrogenase subunit 1, human