Published online April 30, 2007
doi:10.1083/jcb.200610042
The Journal of Cell Biology, Vol. 177, No. 3, 439-450
The Rockefeller University Press, 0021-9525 $30.00
© 2007 Wasiak et al.
Bax/Bak promote sumoylation of DRP1 and its stable association with mitochondria during apoptotic cell death
Sylwia Wasiak,
Rodolfo Zunino, and
Heidi M. McBride
University of Ottawa Heart Institute, Ottawa, Ontario K1Y 4W7, Canada
Correspondence to Heidi M. McBride: hmcbride{at}ottawaheart.ca
Dynamin-related protein 1 (DRP1) plays an important role in mitochondrial fission at steady state and during apoptosis. Using fluorescence recovery after photobleaching, we demonstrate that in healthy cells, yellow fluorescent protein (YFP)DRP1 recycles between the cytoplasm and mitochondria with a half-time of 50 s. Strikingly, during apoptotic cell death, YFP-DRP1 undergoes a transition from rapid recycling to stable membrane association. The rapid cycling phase that characterizes the early stages of apoptosis is independent of Bax/Bak. However, after Bax recruitment to the mitochondrial membranes but before the loss of mitochondrial membrane potential, YFP-DRP1 becomes locked on the membrane, resulting in undetectable fluorescence recovery. This second phase in DRP1 cycling is dependent on the presence of Bax/Bak but independent of hFis1 and mitochondrial fragmentation. Coincident with Bax activation, we detect a Bax/Bak-dependent stimulation of small ubiquitin-like modifier-1 conjugation to DRP1, a modification that correlates with the stable association of DRP1 with mitochondrial membranes. Altogether, these data demonstrate that the apoptotic machinery regulates the biochemical properties of DRP1 during cell death.
Abbreviations used in this paper: BMK, baby mouse kidney; DKO, double knockout; DRP1, dynamin-related protein 1; STS, staurosporin; SUMO, small ubiquitin-like modifier; WT, wild type.

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