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http://hdl.handle.net/1942/30267
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DC Field | Value | Language |
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dc.contributor.author | Contino, Sabrina | - |
dc.contributor.author | Porporato, Paolo E | - |
dc.contributor.author | Bird, Matthew | - |
dc.contributor.author | Marinangeli, Claudia | - |
dc.contributor.author | Opsomer, Rémi | - |
dc.contributor.author | Sonveaux, Pierre | - |
dc.contributor.author | Bontemps, Françoise | - |
dc.contributor.author | DEWACHTER, Ilse | - |
dc.contributor.author | Octave, Jean-Noël | - |
dc.contributor.author | Bertrand, Luc | - |
dc.contributor.author | Stanga, Serena | - |
dc.contributor.author | Kienlen-Campard, Pascal | - |
dc.date.accessioned | 2020-01-09T11:21:01Z | - |
dc.date.available | 2020-01-09T11:21:01Z | - |
dc.date.issued | 2017 | - |
dc.date.submitted | 2020-01-09T10:01:08Z | - |
dc.identifier.citation | Frontiers in physiology, 8 (Art N° ARTN 796) | - |
dc.identifier.uri | http://hdl.handle.net/1942/30267 | - |
dc.description.abstract | Mitochondrial dysfunction plays a pivotal role in the progression of Alzheimer's disease (AD), and yet the mechanisms underlying the impairment of mitochondrial function in AD remain elusive. Recent evidence suggested a role for Presenilins (PS1 or PS2) in mitochondrial function. Mutations of PSs, the catalytic subunits of the γ-secretase complex, are responsible for the majority of inherited AD cases (FAD). PSs were shown to be present in mitochondria and particularly enriched in mitochondria-associated membranes (MAM), where PS2 is involved in the calcium shuttling between mitochondria and the endoplasmic reticulum (ER). We investigated the precise contribution of PS1 and PS2 to the bioenergetics of the cell and to mitochondrial morphology in cell lines derived from wild type (PS+/+), PS1/2 double knock-out (PSdKO), PS2KO and PS1KO embryos. Our results showed a significant impairment in the respiratory capacity of PSdKO and PS2KO cells with reduction of basal oxygen consumption, oxygen utilization dedicated to ATP production and spare respiratory capacity. In line with these functional defects, we found a decrease in the expression of subunits responsible for mitochondrial oxidative phosphorylation (OXPHOS) associated with an altered morphology of the mitochondrial cristae. This OXPHOS disruption was accompanied by a reduction of the NAD+/NADH ratio. Still, neither ADP/ATP ratio nor mitochondrial membrane potential (ΔΨ) were affected, suggesting the existence of a compensatory mechanism for energetic balance. We observed indeed an increase in glycolytic flux in PSdKO and PS2KO cells. All these effects were truly dependent on PS2 since its stable re-expression in a PS2KO background led to a complete restoration of the parameters impaired in the absence of PS2. Our data clearly demonstrate here the crucial role of PS2 in mitochondrial function and cellular bioenergetics, pointing toward its peculiar role in the formation and integrity of the electron transport chain. | - |
dc.description.sponsorship | This work was supported by a grant of the Foundation for Research on Alzheimer’s disease (PK-C), by the Interuniversity Attraction Pole Programme-Belgian Sate-Belgian Science Policy (IAP-P7/16 and IAP-P7/13) to J-NO, ID, and PK-C, by the Fondation Médicale Reine Elisabeth (FMRE) to J-NO, ID, and PK-C, by the Action de Recherche Concertée (ARC 14/19-059) to PK-C. | - |
dc.language.iso | en | - |
dc.publisher | FRONTIERS MEDIA SA | - |
dc.rights | 2017 Contino, Porporato, Bird, Marinangeli, Opsomer, Sonveaux, Bontemps, Dewachter, Octave, Bertrand, Stanga and Kienlen-Campard. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. | - |
dc.subject.other | : presenilin | - |
dc.subject.other | mitochondria | - |
dc.subject.other | glycolysis | - |
dc.subject.other | oxidative phosphorylation | - |
dc.subject.other | cellular bioenergetics | - |
dc.subject.other | Alzheimer’s disease | - |
dc.title | Presenilin 2-Dependent Maintenance of Mitochondrial Oxidative Capacity and Morphology | - |
dc.type | Journal Contribution | - |
dc.identifier.volume | 8 | - |
local.bibliographicCitation.jcat | A1 | - |
local.publisher.place | PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND | - |
local.type.refereed | Refereed | - |
local.type.specified | Article | - |
local.bibliographicCitation.artnr | ARTN 796 | - |
dc.source.type | Article | - |
dc.identifier.doi | 10.3389/fphys.2017.00796 | - |
dc.identifier.pmid | 29085303 | - |
dc.identifier.isi | 000412739300002 | - |
dc.identifier.eissn | - | |
local.provider.type | PubMed | - |
local.uhasselt.uhpub | no | - |
item.fullcitation | Contino, Sabrina; Porporato, Paolo E; Bird, Matthew; Marinangeli, Claudia; Opsomer, Rémi; Sonveaux, Pierre; Bontemps, Françoise; DEWACHTER, Ilse; Octave, Jean-Noël; Bertrand, Luc; Stanga, Serena & Kienlen-Campard, Pascal (2017) Presenilin 2-Dependent Maintenance of Mitochondrial Oxidative Capacity and Morphology. In: Frontiers in physiology, 8 (Art N° ARTN 796). | - |
item.fulltext | With Fulltext | - |
item.accessRights | Open Access | - |
item.contributor | Contino, Sabrina | - |
item.contributor | Porporato, Paolo E | - |
item.contributor | Bird, Matthew | - |
item.contributor | Marinangeli, Claudia | - |
item.contributor | Opsomer, Rémi | - |
item.contributor | Sonveaux, Pierre | - |
item.contributor | Bontemps, Françoise | - |
item.contributor | DEWACHTER, Ilse | - |
item.contributor | Octave, Jean-Noël | - |
item.contributor | Bertrand, Luc | - |
item.contributor | Stanga, Serena | - |
item.contributor | Kienlen-Campard, Pascal | - |
crisitem.journal.eissn | 1664-042X | - |
Appears in Collections: | Research publications |
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File | Description | Size | Format | |
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fphys-08-00796.pdf | Published version | 3.05 MB | Adobe PDF | View/Open |
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