Is supercomplex organization of the respiratory chain required for optimal electron transfer activity?

AbstractThe supra-molecular assembly of the main respiratory chain enzymatic complexes in the form of “supercomplexes” has been proved by structural and functional experimental evidence. This evidence strongly contrasts the previously accepted Random Diffusion Model stating that the complexes are functionally connected by lateral diffusion of small redox molecules (i.e. Coenzyme Q and cytochrome c).This review critically examines the available evidence and provides an analysis of the functional consequences of the intermolecular association of the respiratory complexes pointing out the role of Coenzyme Q and of cytochrome c as channeled or as freely diffusing intermediates in the electron transfer activity of their partner enzymes

Characterisation of the supramolecular organisation of the mitochondrial respiratory chain: a methodological approach by Metabolic Control Analysis.

We have exploited metabolic flux control analysis to differentiate between randomly distributed respiratory complexes and substrate channelling in supercomplexes in mitochondria. Blue-native gel electrophoresis shows supercomplexes comprising Complexes I, III and IV in most systems examined, however our flux control studies demonstrated that electron channelling occurs only between Complexes I and III in mammalian mitochondria, whereas Complex IV is functionally distinct and is fed electrons by the pool behaviour of cytochrome c. This is at difference with plant mitochondria where Complexes I, III and IV represent a single functional unit. The stability of supercomplexes is dictated by the lipid content and is strongly decreased by lipid peroxidation

Incidence and progression to cirrhosis of new hepatitis C virus infections in persons living with human immunodeficiency virus

Objective: To estimate the incidence of hepatitis C virus (HCV) seroconversion and the risk of severe fibrosis/cirrhosis in HCV seroconverters among persons with human immunodeficiency virus (HIV) infection. Methods: We analysed data on 4059 persons with HIV enrolled in a cohort study in Italy. Results: Incidence rate of seroconversion was 0.6/100 person-years overall, and drug users and menwho-have-sex-with-men were at highest risk. The cumulative risk of progression to severe fibrosis/cirrhosis was 30% by 10 years after seroconversion. Conclusions: New HCV infections have a rapidly progressive course in this population. Persons with HIV and HCV superinfection should be prioritized for treatment with anti-HCV direct-acting antivirals

Human immunodeficiency virus continuum of care in 11 european union countries at the end of 2016 overall and by key population: Have we made progress?

Background. High uptake of antiretroviral treatment (ART) is essential to reduce human immunodeficiency virus (HIV) transmission and related mortality; however, gaps in care exist. We aimed to construct the continuum of HIV care (CoC) in 2016 in 11 European Union (EU) countries, overall and by key population and sex. To estimate progress toward the Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 target, we compared 2016 to 2013 estimates for the same countries, representing 73% of the population in the region. Methods. A CoC with the following 4 stages was constructed: number of people living with HIV (PLHIV); proportion of PLHIV diagnosed; proportion of those diagnosed who ever initiated ART; and proportion of those ever treated who achieved viral suppression at their last visit. Results. We estimated that 87% of PLHIV were diagnosed; 92% of those diagnosed had ever initiated ART; and 91% of those ever on ART, or 73% of all PLHIV, were virally suppressed. Corresponding figures for men having sex with men were: 86%, 93%, 93%, 74%; for people who inject drugs: 94%, 88%, 85%, 70%; and for heterosexuals: 86%, 92%, 91%, 72%. The proportion suppressed of all PLHIV ranged from 59% to 86% across countries. Conclusions. The EU is close to the 90-90-90 target and achieved the UNAIDS target of 73% of all PLHIV virally suppressed, significant progress since 2013 when 60% of all PLHIV were virally suppressed. Strengthening of testing programs and treatment support, along with prevention interventions, are needed to achieve HIV epidemic control