FAD Synthesis and Degradation in the Nucleus Create a Local Flavin Cofactor Pool

Giancaspero, Teresa Anna; Busco, Giovanni; Panebianco, Concetta; Carmone, Claudia; Miccolis, Angelica; Liuzzi, Grazia Maria; Colella, Matilde; Barile, Maria

doi:10.1074/jbc.m113.500066

Cited by 74 publications

(60 citation statements)

References 58 publications

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“…Intracellular FAD is produced from riboflavins (vitamin B2) and ATP, and has been found in the cytoplasm, the mitochondria, and the nucleus (Giancaspero et al, 2013). FAD is reduced to FADH 2 during the conversion of acyl-CoA to 2-enoyl-CoA in FAO, and by complex II (succinate dehydrogenase) in the mitochondria.…”

Section: The Role Of Metabolites In Epigenetic Regulation Of Transcrimentioning

confidence: 99%

Metabolic Reprogramming of Stem Cell Epigenetics

et al. 2015

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Summary For many years, stem cell metabolism was viewed as a by product of cell fate status rather than an active regulatory mechanism, however there is now a growing appreciation that metabolic pathways influence epigenetic changes associated with lineage commitment, specification, and self-renewal. Here we review how metabolites generated during glycolytic and oxidative processes are utilized in enzymatic reactions leading to epigenetic modifications and transcriptional regulation. We discuss how “metabolic reprogramming” contributes to global epigenetic changes in the context of naïve and primed pluripotent states, somatic reprogramming, and hematopoietic and skeletal muscle tissue stem cells, and the implications for regenerative medicine.

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Section: The Role Of Metabolites In Epigenetic Regulation Of Transcrimentioning

confidence: 99%

Metabolic Reprogramming of Stem Cell Epigenetics

et al. 2015

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“…Briefly, in a stoichiometric ratio of 2Fe 3+ :Fe 2+ , 16 mmol (2.66 g) FeCl 3 and 8 mmol (1.63 g) FeCl 2 ·4H 2 O dissolved in 190 mL de-ionized water were co-precipitated using 10 mL 25% NH 3 . The nanoparticles Nano Res.…”

Section: Synthesis Of Iron Oxide Nanoparticles (Fe 3 O 4 )mentioning

confidence: 99%

“…Vitamins have been studied in the context of diagnostic and therapeutic agents because they are biocompatible, endogenously accessible, act as carriers, strongly bind to respective receptors, and mediate important cellular metabolic functions [1][2][3]. Their pivotal role in the prevention and treatment of different types of cancer has been explored in various clinical trials, thus promoting the development of vitamin-based drugs and imaging agents [4,5].…”

Section: Introductionmentioning

confidence: 99%

In vivo evaluation of riboflavin receptor targeted fluorescent USPIO in mice with prostate cancer xenografts

et al. 2016

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Riboflavin (Rf) receptors bind and translocate Rf and its phosphorylated forms (e.g. flavin mononucleotide, FMN) into cells where they mediate various cellular metabolic pathways. Previously, we showed that FMN-coated ultrasmall superparamagnetic iron oxide (FLUSPIO) nanoparticles are suitable for labeling metabolically active cancer and endothelial cells in vitro. In this study, we focused on the in vivo application of FLUSPIO using prostate cancer xenografts. Size, charge, and chemical composition of FLUSPIO were evaluated. We explored the in vitro specificity of FLUSPIO for its cellular receptors using magnetic resonance imaging (MRI) and Prussian blue staining. Competitive binding experiments were performed in vivo by injecting free FMN in excess. Bio-distribution of FLUSPIO was determined by estimating iron content in organs and tumors using a colorimetric assay. AFM analysis and zeta potential measurements revealed a particulate morphology approximately 20-40 nm in size and a negative zeta potential (-24.23 ± 0.15 mV) in water. X-ray photoelectron spectroscopy and time-of-flight secondary ion mass spectrometry data confirmed FMN present on the USPIO nanoparticle surface. FLUSPIO uptake in prostate cancer cells and human umbilical vein endothelial cells was significantly higher than that of control USPIO, while addition of excess of free FMN reduced accumulation. Similarly, in vivo MRI and histology showed specific FLUSPIO uptake by prostate cancer cells, tumor endothelial cells, and tumor-associated macrophages. Besides prominent tumor accumulation, FLUSPIO accumulated in the liver, spleen, lung, and skin. Hence, our data strengthen our hypothesis that targeting riboflavin receptors is an efficient approach to accumulate nanomedicines in tumors opening perspectives for the development of diagnostic and therapeutic systems.

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“…The Ki value of NAD + was one order of magnitude lower than that of NADH. A nuclear pool of FAD and FAD metabolizing enzymes was observed in rat liver; and the nuclear FAD pyrophosphatase could be also inhibited by adenylate-containing nucleotides [102]. Further research is needed to 14 explore the regulation of luminal FAD pool in the ER [103] and its physiological implications.…”

Section: Flavin Nucleotidesmentioning

confidence: 99%