OPA1 alternate splicing uncouples an evolutionary conserved function in mitochondrial fusion from a vertebrate restricted function in apoptosis.: OPA1 isoforms in mitochondrial fusion or apoptosis
Autor: | Pascale Belenguer, Laurent Baricault, Cécile Delettre, Aurélien Olichon, Ghizlane Elachouri, Guy Lenaers |
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Přispěvatelé: | Laboratoire de Biologie Cellulaire et Moléculaire du Contrôle de la Prolifération (LBCMCP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie et thérapie des déficits sensoriels et moteurs, Université Montpellier 2 - Sciences et Techniques (UM2)-IFR76-Institut National de la Santé et de la Recherche Médicale (INSERM) |
Rok vydání: | 2006 |
Předmět: |
fusion
Mitochondrion Biology OPA1 GTP Phosphohydrolases Evolution Molecular Mitochondrial Proteins 03 medical and health sciences Exon 0302 clinical medicine Sequence Analysis Protein Yeasts Protein Interaction Mapping Tumor Cells Cultured Animals Humans Protein Isoforms Molecular Biology 030304 developmental biology Dynamin Genetics 0303 health sciences Alternative splicing apoptosis alternate splicing Cell Biology Cell biology mitochondria Alternative Splicing Microscopy Fluorescence mitochondrial fusion Mitochondrial Membranes RNA splicing [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] Mitochondrial fission 030217 neurology & neurosurgery Function (biology) HeLa Cells |
Zdroj: | Cell Death and Differentiation Cell Death and Differentiation, Nature Publishing Group, 2007, 14 (4), pp.682-92. ⟨10.1038/sj.cdd.4402048⟩ |
ISSN: | 1476-5403 1350-9047 |
DOI: | 10.1038/sj.cdd.4402048 |
Popis: | In most eucaryote cells, release of apoptotic proteins from mitochondria involves fission of the mitochondrial network and drastic remodelling of the cristae structures. The intramitochondrial dynamin OPA1, as a potential central actor of these processes, exists as eight isoforms resulting from the alternate splicing combinations of exons (Ex) 4, 4b and 5b, which functions remain undetermined. Here, we show that Ex4 that is conserved throughout evolution confers functions to OPA1 involved in the maintenance of the DeltaPsi(m) and in the fusion of the mitochondrial network. Conversely, Ex4b and Ex5b, which are vertebrate specific, define a function involved in cytochrome c release, an apoptotic process also restricted to vertebrates. The drastic changes of OPA1 variant abundance in different organs suggest that nuclear splicing can control mitochondrial dynamic fate and susceptibility to apoptosis and pathologies. |
Databáze: | OpenAIRE |
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