MAPL SUMOylation of Drp1 Stabilizes an ER/Mitochondrial Platform Required for Cell Death.

TitleMAPL SUMOylation of Drp1 Stabilizes an ER/Mitochondrial Platform Required for Cell Death.
Publication TypeJournal Article
Year of Publication2015
AuthorsPrudent, J, Zunino, R, Sugiura, A, Mattie, S, Shore, GC, McBride, HM
JournalMol Cell
Volume59
Issue6
Pagination941-55
Date Published2015 Sep 17
ISSN1097-4164
KeywordsApoptosis, bcl-2 Homologous Antagonist-Killer Protein, bcl-2-Associated X Protein, Calcium Signaling, Cysteine Endopeptidases, Endoplasmic Reticulum, GTP Phosphohydrolases, HeLa Cells, Humans, Microtubule-Associated Proteins, Mitochondria, Mitochondrial Proteins, Peptide Hydrolases, Protein Transport, Signal Transduction, Sumoylation, Ubiquitin-Protein Ligases
Abstract

There has been evidence that mitochondrial fragmentation is required for apoptosis, but the molecular links between the machinery regulating dynamics and cell death have been controversial. Indeed, activated BAX and BAK can form functional channels in liposomes, bringing into question the contribution of mitochondrial dynamics in apoptosis. We now demonstrate that the activation of apoptosis triggers MAPL/MUL1-dependent SUMOylation of the fission GTPase Drp1, a process requisite for cytochrome c release. SUMOylated Drp1 functionally stabilizes ER/mitochondrial contact sites that act as hotspots for mitochondrial constriction, calcium flux, cristae remodeling, and cytochrome c release. The loss of MAPL does not alter the activation and assembly of BAX/BAK oligomers, indicating that MAPL is activated downstream of BAX/BAK. This work demonstrates how interorganellar contacts are dynamically regulated through active SUMOylation during apoptosis, creating a stabilized platform that signals cytochrome c release.

DOI10.1016/j.molcel.2015.08.001
Alternate JournalMol. Cell
Citation Key10.1016/j.molcel.2015.08.001
PubMed ID26384664
Grant ListMFE-140925 / / Canadian Institutes of Health Research / Canada
MOP#6192 / / Canadian Institutes of Health Research / Canada
MOP#68833 / / Canadian Institutes of Health Research / Canada