Impaired mitochondrial oxidative phosphorylation in the peroxisomal disease X-linked adrenoleukodystrophy

This is a pre-copyedited, author-produced PDF of an article accepted for publication in Human Molecular Genetics following peer review. The version of record Human Molecular Genetics 22.16 (2013): 3296-3305 is available online at http://hmg.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=23604518X-linked adrenoleukodystrophy (X-ALD) is an inherited metabolic disorder of the nervous system characterized by axonopathy in spinal cords and/or cerebral demyelination, adrenal insufficiency and accumulation of very long-chain fatty acids (VLCFAs) in plasma and tissues. The disease is caused by malfunction of the ABCD1 gene, which encodes a peroxisomal transporter of VLCFAs or VLCFA-CoA. In the mouse, Abcd1 loss causes late onset axonal degeneration in the spinal cord, associated with locomotor disability resembling the most common phenotype in patients, adrenomyeloneuropathy. We have formerly shown that an excess of the VLCFA C26:0 induces oxidative damage, which underlies the axonal degeneration exhibited by the Abcd1(-) mice. In the present study, we sought to investigate the noxious effects of C26:0 on mitochondria function. Our data indicate that in X-ALD patients' fibroblasts, excess of C26:0 generates mtDNA oxidation and specifically impairs oxidative phosphorylation (OXPHOS) triggering mitochondrial ROS production from electron transport chain complexes. This correlates with impaired complex V phosphorylative activity, as visualized by high-resolution respirometry on spinal cord slices of Abcd1(-) mice. Further, we identified a marked oxidation of key OXPHOS system subunits in Abcd1(-) mouse spinal cords at presymptomatic stages. Altogether, our results illustrate some of the mechanistic intricacies by which the excess of a fatty acid targeted to peroxisomes activates a deleterious process of oxidative damage to mitochondria, leading to a multifaceted dysfunction of this organelle. These findings may be of relevance for patient management while unveiling novel therapeutic targets for X-ALDThis study was supported by grants from the European Commission (FP7-241622), the European Leukodystrophy Association (ELA2009-036C5; ELA2008-040C4), the Spanish Institute for Health Carlos III (FIS PI080991 and FIS PI11/01043), the Autonomous Government of Catalonia (2009SGR85) to A.P. and the Spanish Institute for Health Carlos III (Miguel Servet program CP11/00080) to S.F. The CIBER on Rare Diseases (CIBERER) is an initiative of the ISCIII. The study was developed under the COST action BM0604 (to A.P.). J.L.-E. was a fellow of the Department of Education, Universities and Research of the Basque Country Government (BFI07.126). S.F. was a fellow of the European Leukodystrophy Association (ELA 2010-020F1). The studies conducted at the Department of Experimental Medicine were supported in part by R&D grants from the Spanish Ministry of Science and Innovation (BFU2009-11879/BFI), the Spanish Ministry of Health (PI11/1532), the Autonomous Government of Catalonia (2009SGR735), the ‘La Caixa’ Foundation and COST B35 Action of the European Union. D.C. is a fellow from the Spanish Ministry of Health (FI08-00707). The studies conducted at the Department of Biochemistry and Molecular Biology, University of Barcelona, were supported by grants SAF2008-01896 and SAF2011-23636 from the Spanish Ministry of Science and Innovatio

Centralized Control in Photovoltaic Distributed Maximum Power Point Tracking Systems

Photovoltaic energy harvest in distributed maximum power point tracking systems has demonstrated to be superior to the traditional photovoltaic systems under mismatch conditions. The distributed architecture usually consists of series-connected DC/DC converters forming a string, dedicated to process the power of individual photovoltaic panels. However, the classical approach assumes an independent control of the DC/DC converters preventing them from knowing the operating condition of the other converters in the string. The adoption of centralized algorithms allows full control of the variables in distributed maximum power point tracking systems and hence further increases the energy harvest. This paper proposes a novel centralized control that matches distributed and central maximum power point tracking functions, as well as an innovative functionality that improves the dynamic performance in photovoltaic applications.info:eu-repo/semantics/publishe

Impaired mitochondrial oxidative phosphorylation in the peroxisomal disease X-linked adrenoleukodystrophy

X-linked adrenoleukodystrophy (X-ALD) is an inherited metabolic disorder of the nervous systemcharacterized by axonopathy in spinal cords and/or cerebral demyelination, adrenal insufficiency and accumulation of very long-chain fatty acids (VLCFAs) in plasma and tissues. The disease is caused by malfunction of the ABCD1 gene, which encodes a peroxisomal transporter of VLCFAs or VLCFA-CoA. In the mouse, Abcd1 loss causes late onset axonal degeneration in the spinal cord, associated with locomotor disability resembling the most common phenotype in patients, adrenomyeloneuropathy. We have formerly shown that an excess of the VLCFA C26:0 induces oxidative damage, which underlies the axonal degeneration exhibited by the Abcd1- mice. In the present study, we sought to investigate the noxious effects of C26:0 on mitochondria function. Ourdata indicate that in X-ALDpatients' fibroblasts,excessof C26:0 generatesmt DNA oxidation and specifically impairs oxidative phosphorylation (OXPHOS) triggering mitochondrialROSproduction from electron transport chain complexes. This correlates with impaired complex V phosphorylative activity, as visualized by high-resolution respirometry on spinal cord slices of Abcd1- mice. Further, we identified a marked oxidation of key OXPHOS system subunits in Abcd1- mouse spinal cords at presymptomatic stages. Altogether, our results illustratesomeof themechanistic intricacies bywhichthe excessof a fatty acid targeted to peroxisomesactivates a deleterious process of oxidative damage to mitochondria, leading to amultifaceted dysfunction of this organelle. These findings may be of relevance for patient management while unveiling novel therapeutic targets for X-ALD. © The Author 2013. Published by Oxford University Press. All rights reserved.European Commission (FP7-241622); European Leukodystrophy Association (ELA2009-036C5, ELA2008-040C4, ELA 2010-020F1); Spanish Institute for Health Carlos III (FIS PI080991 and FIS PI11/01043); Autonomous Government of Catalonia (2009SGR85); Spanish Institute for Health Carlos III (Miguel Servet program CP11/00080); CIBER on Rare Diseases (CIBERER); COST action BM0604 ; Department of Education, Universities and Research of the Basque Country Government (BFI07.126); European Leukodystrophy Association ; Spanish Ministry of Science and Innovation (BFU2009-11879/BFI); Spanish Ministry of Health (PI11/1532); the Autonomous Government of Catalonia (2009SGR735); the ‘La Caixa’ Foundation and COST B35 Action of the European Union. D.C. is a fellow from the Spanish Ministry of Health (FI08-00707); SAF2008-01896 and SAF2011-23636 from the Spanish Ministry of Science and InnovationPeer Reviewe

Photovoltaic module cascaded converters for distributed maximum power point tracking: A review

© The Institution of Engineering and Technology 2020 Operating photovoltaic (PV) systems under partial shading conditions results in significant power losses. To mitigate partial shading effects, distributed maximum power point tracking (DMPPT) architectures have been proposed. An emerging DMPPT technique represented by PV module cascaded converters (MCCs) has been widely reported in the literature. In this architecture, a DC converter is allocated for each PV module to process and maximise its power. In this sense, mismatch effects are mitigated between PV modules. While MCC architecture has prominent advantages and value-added features, its challenges and limitations cannot be ignored. This study presents a comprehensive review of the state of the art of PV MCC architecture to help readers realise the progress of this DMPPT technique. Several points are extensively discussed and analysed including concept realisation and analysis, DC converter topologies and design optimisation, DMPPT performance limitations, DMPPT control, and protection. The main concepts are reemphasised through a set of simulations. Finally, a list of potential research areas in this field is introduced