title: Lin28A induces energetic switching to glycolytic metabolism in human embryonic kidney cells.
abstract: BACKGROUND
  Loss of a cell's capacity to generate sufficient energy for cellular functions is a key hallmark of the ageing process and ultimately leads to a variety of important age-related pathologies such as cancer, Parkinson's disease and atherosclerosis. Regenerative medicine has sought to reverse these pathologies by reprogramming somatic cells to a more juvenile energetic state using a variety of stem cell factors. One of these factors, Lin28, is considered a candidate for modification in the reprogramming of cellular energetics to ameliorate the ageing process while retaining cell phenotype.
  
  
  RESULTS
  Over-expression of Lin28A resulted in key changes to cellular metabolism not observed in wild-type controls. Extracellular pH flux analysis indicated that Lin28A over expression significantly increased the rate of glycolysis, whilst high resolution oxygen respirometry demonstrated a reduced oxygen consumption. Western blot and real-time PCR analysis identified Hexokinase II as one of the key modulators of glycolysis in these cells which was further confirmed by increased glucose transport. A metabolic switching effect was further emphasised by Western blot analysis where the oxygen consuming mitochondrial complex IV was significantly reduced after Lin28A over expression.
  
  
  CONCLUSIONS
  Results from this study confirm that Lin28A expression promotes metabolic switching to a phenotype that relies predominantly on glycolysis as an energy source, while compromising oxidative phosphorylation. Mechanisms to augment regulated Lin28A in age related pathologies that are characterised by mitochondria dysfunction or in differentiated and aged post-mitotic cells is the future goal of this work.
authors.affiliation: Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8TA, Scotland, UK.
authors.forename: Craig K
authors.initials: CK
authors.lastname: Docherty
authors.affiliation: Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8TA, Scotland, UK.
authors.forename: Ian P
authors.initials: IP
authors.lastname: Salt
authors.affiliation: Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8TA, Scotland, UK. John.Mercer@glasgow.ac.uk.|BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, G12 8TA, Scotland, UK. John.Mercer@glasgow.ac.uk.
authors.forename: John R
authors.initials: JR
authors.lastname: Mercer
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003576:Electron Transport Complex IV / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005947:Glucose / Q000235:genetics / Q000494:pharmacology; D006019:Glycolysis / Q000187:drug effects / Q000235:genetics*; D057809:HEK293 Cells; D006593:Hexokinase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009840:Oligomycins / Q000494:pharmacology; D010085:Oxidative Phosphorylation / Q000187:drug effects; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C516326:LIN28B protein, human; D009840:Oligomycins; D016601:RNA-Binding Proteins; D003576:Electron Transport Complex IV; C000609700:HK2 protein, human; D006593:Hexokinase; D005947:Glucose
keywords: Cellular metabolism; Glycolysis; Hexokinase II; Lin28; Reprogramming