Presenilin 2 Modulates Endoplasmic Reticulum-Mitochondria Coupling by Tuning the Antagonistic Effect of Mitofusin 2
Communication between organelles plays key roles in cell biology. In particular, physical and functional coupling of the endoplasmic reticulum (ER) and mitochondria is crucial for regulation of various physiological and pathophysiological processes. Here, we demonstrate that Presenilin 2 (PS2), muta...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2016-06-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124716305800 |
| _version_ | 1818042193607131136 |
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| author | Riccardo Filadi Elisa Greotti Gabriele Turacchio Alberto Luini Tullio Pozzan Paola Pizzo |
| author_facet | Riccardo Filadi Elisa Greotti Gabriele Turacchio Alberto Luini Tullio Pozzan Paola Pizzo |
| author_sort | Riccardo Filadi |
| collection | DOAJ |
| description | Communication between organelles plays key roles in cell biology. In particular, physical and functional coupling of the endoplasmic reticulum (ER) and mitochondria is crucial for regulation of various physiological and pathophysiological processes. Here, we demonstrate that Presenilin 2 (PS2), mutations in which underlie familial Alzheimer’s disease (FAD), promotes ER-mitochondria coupling only in the presence of mitofusin 2 (Mfn2). PS2 is not necessary for the antagonistic effect of Mfn2 on organelle coupling, although its abundance can tune it. The two proteins physically interact, whereas their homologues Mfn1 and PS1 are dispensable for this interplay. Moreover, PS2 mutants associated with FAD are more effective than the wild-type form in modulating ER-mitochondria tethering because their binding to Mfn2 in mitochondria-associated membranes is favored. We propose a revised model for ER-mitochondria interaction to account for these findings and discuss possible implications for FAD pathogenesis. |
| first_indexed | 2024-12-10T08:42:26Z |
| format | Article |
| id | doaj.art-2949ced184f94370b7ddf6757664b549 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-10T08:42:26Z |
| publishDate | 2016-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-2949ced184f94370b7ddf6757664b5492022-12-22T01:55:49ZengElsevierCell Reports2211-12472016-06-0115102226223810.1016/j.celrep.2016.05.013Presenilin 2 Modulates Endoplasmic Reticulum-Mitochondria Coupling by Tuning the Antagonistic Effect of Mitofusin 2Riccardo Filadi0Elisa Greotti1Gabriele Turacchio2Alberto Luini3Tullio Pozzan4Paola Pizzo5Department of Biomedical Sciences, University of Padua, via U. Bassi 58/B, Padua 35131, ItalyDepartment of Biomedical Sciences, University of Padua, via U. Bassi 58/B, Padua 35131, ItalyDepartment of Biomedical Sciences, Institute of Protein Biochemistry, Italian National Research Council (CNR), via P. Castellino 111, Naples 80131, ItalyDepartment of Biomedical Sciences, Institute of Protein Biochemistry, Italian National Research Council (CNR), via P. Castellino 111, Naples 80131, ItalyDepartment of Biomedical Sciences, University of Padua, via U. Bassi 58/B, Padua 35131, ItalyDepartment of Biomedical Sciences, University of Padua, via U. Bassi 58/B, Padua 35131, ItalyCommunication between organelles plays key roles in cell biology. In particular, physical and functional coupling of the endoplasmic reticulum (ER) and mitochondria is crucial for regulation of various physiological and pathophysiological processes. Here, we demonstrate that Presenilin 2 (PS2), mutations in which underlie familial Alzheimer’s disease (FAD), promotes ER-mitochondria coupling only in the presence of mitofusin 2 (Mfn2). PS2 is not necessary for the antagonistic effect of Mfn2 on organelle coupling, although its abundance can tune it. The two proteins physically interact, whereas their homologues Mfn1 and PS1 are dispensable for this interplay. Moreover, PS2 mutants associated with FAD are more effective than the wild-type form in modulating ER-mitochondria tethering because their binding to Mfn2 in mitochondria-associated membranes is favored. We propose a revised model for ER-mitochondria interaction to account for these findings and discuss possible implications for FAD pathogenesis.http://www.sciencedirect.com/science/article/pii/S2211124716305800 |
| spellingShingle | Riccardo Filadi Elisa Greotti Gabriele Turacchio Alberto Luini Tullio Pozzan Paola Pizzo Presenilin 2 Modulates Endoplasmic Reticulum-Mitochondria Coupling by Tuning the Antagonistic Effect of Mitofusin 2 Cell Reports |
| title | Presenilin 2 Modulates Endoplasmic Reticulum-Mitochondria Coupling by Tuning the Antagonistic Effect of Mitofusin 2 |
| title_full | Presenilin 2 Modulates Endoplasmic Reticulum-Mitochondria Coupling by Tuning the Antagonistic Effect of Mitofusin 2 |
| title_fullStr | Presenilin 2 Modulates Endoplasmic Reticulum-Mitochondria Coupling by Tuning the Antagonistic Effect of Mitofusin 2 |
| title_full_unstemmed | Presenilin 2 Modulates Endoplasmic Reticulum-Mitochondria Coupling by Tuning the Antagonistic Effect of Mitofusin 2 |
| title_short | Presenilin 2 Modulates Endoplasmic Reticulum-Mitochondria Coupling by Tuning the Antagonistic Effect of Mitofusin 2 |
| title_sort | presenilin 2 modulates endoplasmic reticulum mitochondria coupling by tuning the antagonistic effect of mitofusin 2 |
| url | http://www.sciencedirect.com/science/article/pii/S2211124716305800 |
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