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Mitochondrial bioenergetic profile and metabolic adaptation in human hepatocellular carcinoma cell lines with distinct differentation characteristics
No full textMitochondrial structure and function analysis in human hepatocarcinoma cell lines with different growth/differentiation
No full textMitochondria immunofluorescence and immunoblot analyses in human hepatocarcinoma cell lines with different grade of differentiation
No full textMetabolic plasticity of tumor cells: analysis of ATP synthase and IF1 in the glucose modulation of the oxidative metabolism
No full textMitochondrial bioenergetic profile and metabolic adaptation of human hepatocarcinoma cell lines
No full textF1FO ATP synthase is expressed at the surface of embryonic rat heart-derived H9c2 cells and is affected by cardiac-like differentiation
No full textABSTRACT
Taking advantage from the peculiar features of the embryonic rat heart-derived myoblast cell line H9c2, the present study is the first to provide evidence for the expression of F1FO ATP synthase and of ATPase Inhibitory Factor 1 (IF1) on the surface of cells of cardiac origin, together documenting that they were affected through cardiac-like differentiation. Subunits of both the catalytic F1 sector of the complex (ATP synthase-) and of the peripheral stalk, responsible for the correct F1-FO assembly/coupling, (OSCP, b, F6) were detected by immunofluorescence, together with IF1. The expression of ATP synthase-, ATP synthase-b and F6 were similar for parental and differentiated H9c2, while the levels of OSCP increased noticeably in differentiated cells, where the results of in situ Proximity Ligation Assay were consistent with OSCP interaction within ecto-F1FO complexes. An opposite trend was shown by IF1 whose ectopic expression appeared greater in the parental H9c2. Here, evidence for the IF1 interaction with ecto-F1FO complexes was provided.
Functional analyses corroborate both sets of data. i) An F1FO ATP synthase contribution to the exATP production by differentiated cells suggests an augmented expression of holo-F1FO ATP synthase on plasma membrane, in line with the increase of OSCP expression and interaction considered as a requirement for favouring the F1-FO coupling. ii) The absence of exATP generation by the enzyme, and the finding that exATP hydrolysis was largely oligomycin-insensitive, are in line in parental cells with the deficit of OSCP and suggest the occurrence of sub-assemblies together evoking more regulation by IF1. This article is protected by copyright. All rights reserve
Mitochondrial bioenergetic profile and responses to metabolic inhibition in human hepatocarcinoma cell lines with distinct differentiation characteristics.
No full textThe classical view of tumour cell bioenergetics
has been recently revised. Then, the definition of the
mitochondrial profile is considered of fundamental importance
for the development of anti-cancer therapies, but it still
needs to be clarified. We investigated two human hepatocellular
carcinoma cell lines: the partially differentiated HepG2
and the undifferentiated JHH-6. High resolution respirometry
revealed a marked impairment/uncoupling of OXPHOS
in JHH-6 compared with HepG2, with the phosphorylation
system limiting the capacity for electron transport
much more in JHH-6. Blocking glycolysis or mitochondrial
ATP synthase we demonstrated that in JHH-6 ATP
synthase functions in reverse and consumes glycolytic
ATP, thereby sustaining
Glucose-Modulated Mitochondria Adaptation in Tumor Cells: A Focus on ATP Synthase and Inhibitor Factor 1
No full textWarburg’s hypothesis has been challenged by a number of studies showing that oxidative phosphorylation is repressed in some tumors, rather than being inactive per se. Thus, treatments able to shift energy metabolism by activating mitochondrial pathways have been suggested as an intriguing basis for the optimization of antitumor strategies. In this study, HepG2 hepatocarcinoma cells were cultivated with different metabolic substrates under conditions mimicking “positive” (activation/biogenesis) or “negative” (silencing) mitochondrial adaptation. In addition to the expected up-regulation of mitochondrial biogenesis, glucose deprivation caused an increase in phosphorylating respiration and a rise in the expression levels of the ATP synthase β subunit and Inhibitor Factor 1 (IF1). Hyperglycemia, on the other hand, led to a markedly decreased level of the transcriptional coactivator PGC-α suggesting down-regulation of mitochondrial biogenesis, although no change in mitochondrial mass and no impairment of phosphorylating respiration were observed. Moreover, a reduction in mitochondrial networking and in ATP synthase dimer stability was produced. No effect on β-ATP synthase expression was elicited. Notably, hyperglycemia caused an increase in IF1 expression levels, but it did not alter the amount of IF1 associated with ATP synthase. These results point to a new role of IF1 in relation to high glucose utilization by tumor cells, in addition to its well known effect upon mitochondrial ATP synthase regulation
Interleukin 6, soluble interleukin 2 receptor alpha (CD25), monocyte colony-stimulating factor, and hepatocyte growth factor linked with systemic hyperinflammation, innate immunity hyperactivation, and organ damage in COVID-19 pneumonia
No full textPatients infected by SARS-CoV-2 can develop interstitial pneumonia, requiring hospitalisation or mechanical ventilation. Increased levels of inflammatory biomarkers are associated with development of acute respiratory distress syndrome (ARDS). The aim of the present study was to determine which cytokines are associated with respiratory insufficiency in patients hospitalised for COVID-19
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