Respiratory complex I is essential to induce a Warburg profile in mitochondria-defective tumor cells

Background: Aerobic glycolysis, namely the Warburg effect, is the main hallmark of cancer cells. Mitochondrial respiratory dysfunction has been proposed to be one of the major causes for such glycolytic shift. This hypothesis has been revisited as tumors appear to undergo waves of gene regulation during progression, some of which rely on functional mitochondria. In this framework, the role of mitochondrial complex I is still debated, in particular with respect to the effect of mitochondrial DNA mutations in cancer metabolism. The aim of this work is to provide the proof of concept that functional complex I is necessary to sustain tumor progression. Methods: Complex I-null osteosarcoma cells were complemented with allotopically expressed complex I subunit 1 (MT-ND1). Complex I re-assembly and function recovery, also in terms of NADH consumption, were assessed. Clones were tested for their ability to grow in soft agar and to generate tumor masses in nude mice. Hypoxia levels were evaluated via pimonidazole staining and hypoxia-inducible factor-1\u3b1 (HIF-1\u3b1) immunoblotting and histochemical staining. 454-pyrosequencing was implemented to obtain global transcriptomic profiling of allotopic and non-allotopic xenografts. Results: Complementation of a truncative mutation in the gene encoding MT-ND1, showed that a functional enzyme was required to perform the glycolytic shift during the hypoxia response and to induce a Warburg profile in vitro and in vivo, fostering cancer progression. Such trigger was mediated by HIF-1\u3b1, whose stabilization was regulated after recovery of the balance between \u3b1-ketoglutarate and succinate due to a recuperation of NADH consumption that followed complex I rescue. Conclusion: Respiratory complex I is essential for the induction of Warburg effect and adaptation to hypoxia of cancer cells, allowing them to sustain tumor growth. Differently from other mitochondrial tumor suppressor genes, therefore, a complex I severe mutation such as the one here reported may confer anti-tumorigenic properties, highlighting the prognostic values of such genetic markers in cancer

Near infrared reflectance spectroscopy for estimating soil characteristics valuable in the diagnosis of soil fertility

Soil fertility diagnostics rely not only upon measurement of available nutrients but also upon the soil’s ability to retain these nutrients. Near-infrared reflectance spectroscopy (NIRS) is a rapid and non-destructive analytical technique which allows to simultaneously estimate standard soil characteristics and does not require use of chemicals. Previous studies showed that NIRS could be used in local contexts to predict soil properties. The main goal of our research is to build a methodological framework for the use of NIRS at a more global scale. The specific goals of this study were (i) to identify the best spectra treatment and processing –LOCAL versus GLOBAL regression- methods, (ii) to compare NIRS performances to standard chemical protocols and (iii) to evaluate the ability of NIRS to predict soil total organic carbon (TOC), total Nitrogen (TN), clay content and cationic exchange capacity (CEC) for a wide range of soil conditions. We scanned 1,300 samples representative of main soil types of Wallonia under crop, grassland or forest. Various sample preparations were tested prior to NIRS measurements. The most appropriate options were selected according to ANOVA analysis and multiple means comparisons of the spectra principal components. Fifteen pre-treatments were applied to a calibration set and the prediction accuracy was evaluated for GLOBAL and LOCAL modified partial least square (MPLS) regression models. The LOCAL MPLS calibrations showed very encouraging results for all the studied characteristics. On average, for crop soil samples, the prediction coefficient of variation (CVp) was close to 15% for TOC content, 7% for TN content, and 10% for clay content and CEC. The comparisons of repeatability and reproducibility of both NIRS and standard methods showed that NIRS is as reliable as reference methods. Prediction accuracy and technique repeatability allow the use of NIRS within the framework of the soil fertility evaluation and its replacement of standard protocols. LOCAL MPLS can be applied within global datasets, such as the International global soil spectral library. However, the performance of LOCAL MPLS is linked to the number of similar spectra in the dataset and more standard measurements are needed to characterize the least widespread soils