RNAase III-Type Enzyme Dicer Regulates Mitochondrial Fatty Acid Oxidative Metabolism in Cardiac Mesenchymal Stem Cells

• Published in: International journal of molecular sciences Vol. 20; no. 22; p. 5554
• Main Authors: Su, Xuan, Jin, Yue, Shen, Yan, Kim, Il-Man, Weintraub, Neal L, Tang, Yaoliang
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 07.11.2019; MDPI
• Subjects: Ablation; Acyl-CoA oxidase; Adenoviruses; aerobic glycolysis; Animals; Apoptosis; Cardiac function; cardiac mesenchymal stem cells (c-msc); Cell differentiation; Cell growth; Cell proliferation; Citric Acid Cycle; Coenzyme A; Cytoplasm; DEAD-box RNA Helicases - genetics; DEAD-box RNA Helicases - metabolism; Dehydrogenases; dicer; Disease control; Down-regulation; Electron Transport Chain Complex Proteins - genetics; Electron Transport Chain Complex Proteins - metabolism; Energy metabolism; Enzymes; Fatty acids; Fatty Acids - genetics; Fatty Acids - metabolism; Gene Deletion; Gene expression; Genes; Glycolysis; Heart diseases; Heart failure; Humans; Maturation; Mesenchymal stem cells; Mesenchymal Stem Cells - enzymology; Metabolism; Mice; MicroRNAs; miRNA; Mitochondria; Mitochondria, Heart - genetics; Mitochondria, Heart - metabolism; Mitochondrial DNA; mitochondrial oxidative metabolism; Myocardium - enzymology; Oxidase; Oxidation; Oxidation-Reduction; Oxidative metabolism; Oxidative stress; Phosphorylation; Respiration; Ribonuclease III; Ribonuclease III - genetics; Ribonuclease III - metabolism; RNA, Transfer, Thr; RNA-induced silencing complex; RNA-mediated interference; siRNA; SIRT1 protein; Stem cell transplantation; Stem cells; Substrates; Transcription factors; Transfection; warburg effect; β-oxidation; β-oxidation; dicer; cardiac mesenchymal stem cells (C-MSC); mitochondrial oxidative metabolism; aerobic glycolysis; Warburg effect
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20225554

Cardiac mesenchymal stem cells (C-MSC) play a key role in maintaining normal cardiac function under physiological and pathological conditions. Glycolysis and mitochondrial oxidative phosphorylation predominately account for energy production in C-MSC. Dicer, a ribonuclease III endoribonuclease, plays a critical role in the control of microRNA maturation in C-MSC, but its role in regulating C-MSC energy metabolism is largely unknown. In this study, we found that Dicer knockout led to concurrent increase in both cell proliferation and apoptosis in C-MSC compared to Dicer floxed C-MSC. We analyzed mitochondrial oxidative phosphorylation by quantifying cellular oxygen consumption rate (OCR), and glycolysis by quantifying the extracellular acidification rate (ECAR), in C-MSC with/without Dicer gene deletion. Dicer gene deletion significantly reduced mitochondrial oxidative phosphorylation while increasing glycolysis in C-MSC. Additionally, Dicer gene deletion selectively reduced the expression of β-oxidation genes without affecting the expression of genes involved in the tricarboxylic acid (TCA) cycle or electron transport chain (ETC). Finally, Dicer gene deletion reduced the copy number of mitochondrially encoded 1,4-Dihydronicotinamide adenine dinucleotide (NADH): ubiquinone oxidoreductase core subunit 6 (MT-ND6), a mitochondrial-encoded gene, in C-MSC. In conclusion, Dicer gene deletion induced a metabolic shift from oxidative metabolism to aerobic glycolysis in C-MSC, suggesting that Dicer functions as a metabolic switch in C-MSC, which in turn may regulate proliferation and environmental adaptation.