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Succinate dehydrogenase (also known as complex II) plays a dual role in respiration by catalyzing the oxidation of succinate to fumarate in the tricarboxylic acid (TCA) cycle and transferring electrons from succinate to ubiquinone in the mitochondrial electron transport chain (ETC). Owing to the privileged position of SDH/CII, its dysfunction leads to TCA cycle arrest and altered respiration. This review aims to elucidate the widely documented profound metabolic effects of SDH/CII deficiency, along with the newly unveiled survival mechanisms in SDH/CII-deficient cells. Such an understanding reveals exploitable vulnerabilities for strategic targeting, which is crucial for the development of novel and more precise therapies for primary mitochondrial diseases, as well as for familial and sporadic cancers associated with SDH/CII mutations. [ABSTRACT FROM AUTHOR]

Background: There is a high prevalence of metabolic syndrome in Western societies, and it is therefore an example of chronic disease whose follow-up could be enhanced by telemedicine.Objective: The objective of this study was to assess the effectiveness of a telemedicine programme for the follow-up and control of patients with metabolic syndrome in a primary-care setting.Methods: Semi-experimental study in which 82 patients with metabolic syndrome were included in a telemedicine programme and compared to 82 patients routinely followed up at health-care facilities. The programme consisted of the teletransmission of analytical parameters via the PITES technological platform for chronic and dependent patients. Other study variables were lifestyle, treatment compliance, perceived health status and satisfaction with the programme.Results: Follow-up showed that 68 patients (82.9%) continued in the programme after 6 months and 45 (54.9%) after one year, with a mean stay of 39.7 weeks. Comparison of the parameters obtained for the telemedicine and control-group patients indicated that the former registered significantly lower mean values for systolic blood pressure (125.5 ± 10.6 SD vs. 136.7 ± 12.0 SD), diastolic blood pressure (81.0 ± 6.3 SD vs. 84.0 ± 6.8 SD), total cholesterol (177.4 ± 34.5 SD vs. 202.4 ± 31.7 SD) and cLDL (106.0 ± 28.1 SD vs. 121.3 ± 30.6 SD). By the end of follow-up, the health status scores of the patients monitored by telemedicine had risen significantly (69.2 vs. 64.2; p=0.04), and 86.6% stated that they were satisfied.Conclusions: Telemedicine allows for better control of some of the defining parameters of metabolic syndrome than is achieved by routine clinical practice. Teletransmission is viable and satisfactory, and constitutes a novel contribution to the clinical management of these patients. [ABSTRACT FROM AUTHOR]

We generated Fas-activated serine threonine phosphoprotein (FAST)-deficient mice \((FAST^{−/−})\) to study the in vivo role of FAST in immune system function. In a model of house dust mite-induced allergic pulmonary inflammation, wild type mice develop a mixed cellular infiltrate composed of eosinophils, lymphocytes, and neutrophils. \(FAST^{−/−}\) mice develop airway inflammation that is distinguished by the near absence of neutrophils. Similarly, LPS-induced alveolar neutrophil recruitment is markedly reduced in \(FAST^{−/−}\) mice compared with wild type controls. This is accompanied by reduced concentrations of cytokines (TNF-α and IL-6 and -23) and chemoattractants (MIP-2 and keratinocyte chemoattractant) in bronchoalveolar lavage fluids. Because \(FAST^{−/−}\) neutrophils exhibit normal chemotaxis and survival, impaired neutrophil recruitment is likely to be due to reduced production of chemoattractants within the pulmonary parenchyma. Studies using bone marrow chimeras implicate lung resident hematopoietic cells (e.g., pulmonary dendritic cells and/or alveolar macrophages) in this process. In conclusion, our results introduce FAST as a proinflammatory factor that modulates the function of lung resident hematopoietic cells to promote neutrophil recruitment and pulmonary inflammation.

Phagocytosis is a pivotal process by which innate immune cells eliminate bacteria. In this study, we explore novel regulatory mechanisms of phagocytosis driven by the mitochondria. Fas-activated serine/threonine kinase (FASTK) is an RNA-binding protein with two isoforms, one localized to the mitochondria (mitoFASTK) and the other isoform to cytosol and nucleus. The mitoFASTK isoform has been reported to be necessary for the biogenesis of the mitochondrial ND6 mRNA, which encodes an essential subunit of mitochondrial respiratory complex I (CI, NADH:ubiquinone oxidoreductase). This study investigates the role and the mechanisms of action of FASTK in phagocytosis. Macrophages from FASTK-/- mice exhibited a marked increase in nonopsonic phagocytosis of bacteria. As expected, CI activity was specifically reduced by almost 50% in those cells. To explore if decreased CI activity could underlie the phagocytic phenotype, we tested the effect of CI inhibition on phagocytosis. Indeed, treatment with CI inhibitor rotenone or short hairpin RNAs against two CI subunits (NDUFS3 and NDUFS4) resulted in a marked increase in nonopsonic phagocytosis of bacteria. Importantly, re-expression of mitoFASTK in FASTK-depleted macrophages was sufficient to rescue the phagocytic phenotype. In addition, we also report that the decrease in CI activity in FASTK-/- macrophages is associated with an increase in phosphorylation of the energy sensor AMP-activated protein kinase (AMPK) and that its inhibition using Compound C reverted the phagocytosis phenotype. Taken together, our results clearly demonstrate for the first time, to our knowledge, that mitoFASTK plays a negative regulatory role on nonopsonic phagocytosis of bacteria in macrophages through its action on CI activity. [ABSTRACT FROM AUTHOR]