PMID- 24350892 OWN - NLM STAT- MEDLINE DCOM- 20140919 LR - 20160511 IS - 2152-4998 (Electronic) IS - 2152-4971 (Linking) VI - 16 IP - 1 DP - 2014 Feb TI - Mitochondrial biogenesis and energy production in differentiating murine stem cells: a functional metabolic study. PG - 84-90 LID - 10.1089/cell.2013.0049 [doi] AB - The significance of metabolic networks in guiding the fate of the stem cell differentiation is only beginning to emerge. Oxidative metabolism has been suggested to play a major role during this process. Therefore, it is critical to understand the underlying mechanisms of metabolic alterations occurring in stem cells to manipulate the ultimate outcome of these pluripotent cells. Here, using P19 murine embryonal carcinoma cells as a model system, the role of mitochondrial biogenesis and the modulation of metabolic networks during dimethyl sulfoxide (DMSO)-induced differentiation are revealed. Blue native polyacrylamide gel electrophoresis (BN-PAGE) technology aided in profiling key enzymes, such as hexokinase (HK) [EC 2.7.1.1], glucose-6-phosphate isomerase (GPI) [EC 5.3.1.9], pyruvate kinase (PK) [EC 2.7.1.40], Complex I [EC 1.6.5.3], and Complex IV [EC 1.9.3.1], that are involved in the energy budget of the differentiated cells. Mitochondrial adenosine triphosphate (ATP) production was shown to be increased in DMSO-treated cells upon exposure to the tricarboxylic acid (TCA) cycle substrates, such as succinate and malate. The increased mitochondrial activity and biogenesis were further confirmed by immunofluorescence microscopy. Collectively, the results indicate that oxidative energy metabolism and mitochondrial biogenesis were sharply upregulated in DMSO-differentiated P19 cells. This functional metabolic and proteomic study provides further evidence that modulation of mitochondrial energy metabolism is a pivotal component of the cellular differentiation process and may dictate the final destiny of stem cells. FAU - Han, Sungwon AU - Han S AD - 1 Department of Chemistry and Biochemistry, Laurentian University , Sudbury, Ontario P3E 2C6, Canada . FAU - Auger, Christopher AU - Auger C FAU - Thomas, Sean C AU - Thomas SC FAU - Beites, Crestina L AU - Beites CL FAU - Appanna, Vasu D AU - Appanna VD LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20131219 PL - United States TA - Cell Reprogram JT - Cellular reprogramming JID - 101528176 RN - 0 (Cryoprotective Agents) RN - 0 (Mitochondrial Proteins) RN - YOW8V9698H (Dimethyl Sulfoxide) SB - IM MH - Animals MH - Cell Differentiation/*drug effects MH - Cell Line MH - Cryoprotective Agents/*pharmacology MH - Dimethyl Sulfoxide/*pharmacology MH - Mice MH - Mitochondria/*metabolism MH - Mitochondrial Dynamics/drug effects MH - Mitochondrial Proteins/*biosynthesis MH - Oxidative Phosphorylation/*drug effects MH - Stem Cells EDAT- 2013/12/20 06:00 MHDA- 2014/09/23 06:00 CRDT- 2013/12/20 06:00 PHST- 2013/12/20 06:00 [entrez] PHST- 2013/12/20 06:00 [pubmed] PHST- 2014/09/23 06:00 [medline] AID - 10.1089/cell.2013.0049 [doi] PST - ppublish SO - Cell Reprogram. 2014 Feb;16(1):84-90. doi: 10.1089/cell.2013.0049. Epub 2013 Dec 19.