Riboflavin metabolites are critical components of the mitochondrial electron transport chain. Manole et al. describe the genetics, phenotypes and neuropathology of a large patient series with riboflavin-responsive neuropathy. Using in-vitro and in-vivo models, they reveal mitochondrial dysfunction in the disorder, and validate riboflavin esters as a potential therapeutic strategy.

Background: Folic aid plays an essential role in cellular metabolism. Its deficiency can lead to neural tube defects. However, optimization of body folate homeostasis can reduce the incidence of neural tube defects and may decrease the risk of Alzheimer and cardiovascular diseases and cancer. Hence, food fortification and intake of supplemental folate are widespread. Objective: We examined the effects of long-term folate oversupplementation on the physiologic markers of intestinal and renal folate uptake processes. Design: Human-derived intestinal Caco-2 and renal HK-2 epithelial cells were maintained (5 generations) in a growth medium oversupplemented (100 mol folic acid/L) or maintained under sufficient conditions (0.25 and 9 mol folic acid/L). Results: Carrier-mediated uptake of 3 H-folic acid (2 mol/L) at buffer pH 5.5 (but not buffer pH 7.4) by Caco-2 and HK-2 cells maintained under the folate-oversupplemented condition was significantly (P 0.01) and specifically lower than in cells maintained under the folate-sufficient condition. This reduction in folic acid uptake was associated with a significant decrease in the protein and mRNA levels of the human reduced-folate carrier (hRFC) and a decrease in the activity of the hRFC promoter. It was also associated with a decrease in mRNA levels of the proton-coupled folate transporter/heme carrier protein 1 (PCFT/HCP1) and folate receptor (FR). Conclusions: Long-term oversupplementation with folate leads to a specific and significant down-regulation in intestinal and renal folate uptake, which is associated with a decrease in message levels of hRFC, PCFT/HCP1, and FR. This regulation appears to be mediated via a transcriptional mechanism, at least for the hRFC system.Am J Clin Nutr 2007;86:159 -66.

Microbial fuel cells (MFCs) are emerging as a promising future technology for a wide range of applications in addition to sustainable electricity generation. Electroactive (EA) biofilms produced by microorganisms are the key players in the bioelectrochemical systems involving microorganism mediated electrocatalytic reactions. Therefore, genetically modifying the organism for increased production of EA biofilms and improving the extra electron transfer (EET) mechanisms may attribute to increase in current density of a MFC and an increased COD removal in wastewater treatment plant coupled MFC systems. Extracellular polysaccharides (EPS) produced by the organisms attribute to both biofilm formation and electron transfer. Although cell surface modification, media optimization and operation parameters validation are established as enhancement strategies for a fuel cell performance, engineering the vital genes involved in electroactive biofilm formation is the future hope. Therefore, in this review we critically address the biofilm formation mechanisms in electro active microorganisms, strategies for improving the biofilm formation leading to improved electrocatalytic rates for applications in bioelectrochemical systems.

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