SUMOylation of the mitochondrial fission protein Drp1 occurs at multiple
nonconsensus sites within the B domain and is linked to its activity cycle.
Authors Figueroa-Romero C, Iñiguez-Lluhí JA, Stadler J, Chang CR, Arnoult D, Keller PJ,
Hong Y, Blackstone C, Feldman EL
Submitted By Eva Feldman on 3/24/2010
Status Published
Journal The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Year 2009
Date Published 11/1/2009
Volume : Pages 23(11) : 3917 - 3927
PubMed Reference 19638400
Abstract Dynamin-related protein (Drp) 1 is a key regulator of mitochondrial fission and
is composed of GTP-binding, Middle, insert B, and C-terminal GTPase effector
(GED) domains. Drp1 associates with mitochondrial fission sites and promotes
membrane constriction through its intrinsic GTPase activity. The mechanisms that
regulate Drp1 activity remain poorly understood but are likely to involve
reversible post-translational modifications, such as conjugation of small
ubiquitin-like modifier (SUMO) proteins. Through a detailed analysis, we find
that Drp1 interacts with the SUMO-conjugating enzyme Ubc9 via multiple regions
and demonstrate that Drp1 is a direct target of SUMO modification by all three
SUMO isoforms. While Drp1 does not harbor consensus SUMOylation sequences, our
analysis identified2 clusters of lysine residues within the B domain that serve
as noncanonical conjugation sites. Although initial analysis indicates that
mitochondrial recruitment of ectopically expressed Drp1 in response to
staurosporine is unaffected by loss of SUMOylation, we find that Drp1
SUMOylation is enhanced in the context of the K38A mutation. This
dominant-negative mutant, which is deficient in GTP binding and hydrolysis, does
not associate with mitochondria and prevents normal mitochondrial fission. This
finding suggests that SUMOylation of Drp1 is linked to its activity cycle and is
influenced by Drp1 localization.

Investigators with authorship
Eva FeldmanUniversity of Michigan


Dapk2death-associated kinase 2
Ube2iubiquitin-conjugating enzyme E2I
Dnm1ldynamin 1-like
Racgap1Rac GTPase-activating protein 1
Crmp1collapsin response mediator protein 1