Direct and quantitative analysis of altered metabolic flux distributions and cellular ATP production pathway in fumarate hydratase-diminished cells
SCIENTIFIC REPORTS
Authors: Noguchi, Shingo; Ishikawa, Hirokazu; Wakita, Kenichi; Matsuda, Fumio; Shimizu, Hiroshi
Abstract
Fumarate hydratase (FH) is an enzyme in the tricarboxylic acid (TCA) cycle, biallelic loss-of-function mutations of which are associated with hereditary leiomyomatosis and renal cell cancer. However, how FH defect modulates intracellular metabolic fluxes in human cells has remained unclear. This study aimed to reveal metabolic flux alterations induced by reduced FH activity. We applied C-13 metabolic flux analysis (C-13-MFA) to an established cell line with diminished FH activity (FHdim) and parental HEK293 cells. FHdim cells showed reduced pyruvate import flux into mitochondria and subsequent TCA cycle fluxes. Interestingly, the diminished FH activity decreased FH flux only by about 20%, suggesting a very low need for FH to maintain the oxidative TCA cycle. Cellular ATP production from the TCA cycle was dominantly suppressed compared with that from glycolysis in FHdim cells. Consistently, FHdim cells exhibited higher glucose dependence for ATP production and higher resistance to an ATP synthase inhibitor. In summary, using FHdim cells we demonstrated that FH defect led to suppressed pyruvate import into mitochondria, followed by downregulated TCA cycle activity and altered ATP production pathway balance from the TCA cycle to glycolysis. We confirmed that C-13-MFA can provide direct and quantitative information on metabolic alterations induced by FH defect.
Foliar feeding of boron improves the productivity of cotton cultivars with enhanced boll retention percentage
JOURNAL OF PLANT NUTRITION
Authors: Wahid, Muhammad Ashfaq; Saleem, Muhammad; Irshad, Sohail; Khan, Shahbaz; Cheema, Mumtaz Akhtar; Saleem, Muhammad Farrukh; Tung, Shahbaz Atta
Abstract
Cotton (Gossypium hirsutumL.) is of prime importance because of its quality fiber and edible oil production. Boron (B) is among essential micronutrients for plant growth; it aids in the transfer of sugars and nutrients from leaves to fruit that are involved directly or indirectly in many plant functions. Cotton growth, yield and quality are strongly affected with boron application. A two-year study was conducted to evaluate the impact of foliar applied B (0, 2, 4, 6, 8 and 10 g of B L(-1)of water) on the performance of cotton cultivars (FH-113, MNH-786 and CIM-496). The results indicated that growth, yield and quality traits of cotton were significantly influenced by different levels of foliar applied boron as well as cultivars of cotton. Among cotton cultivars, the yield and quality parameters were superior in cultivar "FH-113." Foliar application of boron at 6 g L(-1)of water improved leaf area index and leaf area duration and eventually improved the number of bolls per plant, boll retention percentage, average boll weight, lint yield, ginning out turn, fiber length and uniformity ratio of cotton. Foliar application of B at 6 g per liter of water, showed promising results by improving growth and quality parameters and is recommend to enhance the economical yield production of cotton cultivar "FH-113" with improved quality.