Chlystun, M;
Campanella, M;
Law, AL;
Duchen, MR;
Fatimathas, L;
Levine, TP;
Gerke, V;
(2013)
Regulation of mitochondrial morphogenesis by annexin a6.
PLoS One
, 8
(1)
, Article e53774. 10.1371/journal.pone.0053774.
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Abstract
Mitochondrial homeostasis is critical in meeting cellular energy demands, shaping calcium signals and determining susceptibility to apoptosis. Here we report a role for anxA6 in the regulation of mitochondrial morphogenesis, and show that in cells lacking anxA6 mitochondria are fragmented, respiration is impaired and mitochondrial membrane potential is reduced. In fibroblasts from AnxA6(-/-) mice, mitochondrial Ca(2+) uptake is reduced and cytosolic Ca(2+) transients are elevated. These observations led us to investigate possible interactions between anxA6 and proteins with roles in mitochondrial fusion and fission. We found that anxA6 associates with Drp1 and that mitochondrial fragmentation in AnxA6(-/-) fibroblasts was prevented by the Drp1 inhibitor mdivi-1. In normal cells elevation of intracellular Ca(2+) disrupted the interaction between anxA6 and Drp1, displacing anxA6 to the plasma membrane and promoting mitochondrial fission. Our results suggest that anxA6 inhibits Drp1 activity, and that Ca(2+)-binding to anxA6 relieves this inhibition to permit Drp1-mediated mitochondrial fission.
| Type: | Article |
|---|---|
| Title: | Regulation of mitochondrial morphogenesis by annexin a6. |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1371/journal.pone.0053774 |
| Publisher version: | http://dx.doi.org/10.1371/journal.pone.0053774 |
| Language: | English |
| Additional information: | © 2013 Chlystun et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This work was supported by grants from the Biotechnology and Biological Sciences Research Council (BBSRC), Wellcome Trust and the DFG. The authors also thank Marie Curie Actions for support to M. Campanella. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/1384617 |
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