Show simple item record

Files in this item


Item metadata

dc.contributor.authorHacker, Christian
dc.contributor.authorHowell, Matthew
dc.contributor.authorBhella, David
dc.contributor.authorLucocq, John Milton
dc.identifier.citationHacker , C , Howell , M , Bhella , D & Lucocq , J M 2014 , ' Strategies for maximizing ATP supply in the microsporidian Encephalitozoon cuniculi : direct binding of mitochondria to the parasitophorous vacuole and clustering of the mitochondrial porin VDAC ' , Cellular Microbiology , vol. 16 , no. 4 , pp. 565-579 .
dc.identifier.otherPURE: 84022758
dc.identifier.otherPURE UUID: 5fb6f883-3d61-48e5-b5f5-feb6da0d1488
dc.identifier.otherPubMed: 24245785
dc.identifier.otherPubMed: 24245785
dc.identifier.otherWOS: 000332950100010
dc.identifier.otherScopus: 84896390333
dc.identifier.otherORCID: /0000-0002-5191-0093/work/64361255
dc.descriptionThe authors were supported by a programme grant from the Wellcome Trust (WT089803MA)en
dc.description.abstractMicrosporidia are obligate intracellular parasites with extremely reduced genomes and a dependence on host-derived ATP. The microsporidium Encephalitozoon cuniculi proliferates within a membranous vacuole and we investigated how the ATP supply is optimized at the vacuole–host interface. Using spatial EM quantification (stereology), we found a single layer of mitochondria coating substantial proportions of the parasitophorous vacuole. Mitochondrial binding occurred preferentially over the vegetative ‘meront’ stages of the parasite, which bulged into the cytoplasm, thereby increasing the membrane surface available for mitochondrial interaction. In a broken cell system mitochondrial binding was maintained and was typified by electron dense structures (< 10 nm long) bridging between outer mitochondrial and vacuole membranes. In broken cells mitochondrial binding was sensitive to a range of protease treatments. The function of directly bound mitochondria, as measured by the membrane potential sensitive dye JC-1, was indistinguishable from other mitochondria in the cell although there was a generalized depression of the membrane potential in infected cells. Finally, quantitative immuno-EM revealed that the ATP-delivering mitochondrial porin, VDAC, was concentrated atthe mitochondria-vacuole interaction site. Thus E. cuniculi appears to maximize ATP supply by direct binding of mitochondria to the parasitophorous vacuole bringing this organelle within 0.020 microns of the growing vegetative form of the parasite. ATP-delivery is further enhanced by clustering of ATP transporting porins in those regions of the outer mitochondrial membrane lying closest to the parasite.
dc.relation.ispartofCellular Microbiologyen
dc.rights© 2013 The Authors. Cellular Microbiology published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.en
dc.subjectAdenosine Triphosphateen
dc.subjectCell Lineen
dc.subjectEncephalitozoon cuniculien
dc.subjectEnergy Metabolismen
dc.subjectImaging, Three-Dimensionalen
dc.subjectMicroscopy, Electronen
dc.subjectVoltage-Dependent Anion Channelsen
dc.subjectQR355 Virologyen
dc.titleStrategies for maximizing ATP supply in the microsporidian Encephalitozoon cuniculi : direct binding of mitochondria to the parasitophorous vacuole and clustering of the mitochondrial porin VDACen
dc.typeJournal articleen
dc.contributor.sponsorThe Wellcome Trusten
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews. School of Medicineen
dc.contributor.institutionUniversity of St Andrews. Biomedical Sciences Research Complexen
dc.description.statusPeer revieweden

This item appears in the following Collection(s)

Show simple item record