Download Rab32 family proteins mediate mitochondria membrane dynamics

P010
Rab32 family proteins mediate mitochondria
membrane dynamics
Thomas Simmen and Carolina Ortiz Sandoval
University of Alberta, Edmonton, Canada
Rab32 is a ubiquitous, but unusual member of the Rab GTPase
family. While it can localize to melanosomes in cells that have
such organelles, endogenous and over-expressed Rab32
localizes primarily to the ER in cells that lack melanosomes.
Here, Rab32 determines the composition of the mitochondriaassociated membrane (MAM), a domain of the ER that mediates
interaction of the secretory pathway with mitochondria. We and
others have published that Rab32 has to be in its GTP-bound,
active state to allow for mitochondrial fission. Consistent with
this, the activity of Rab32 determines apoptosis progression and
ER calcium signaling. Expanding on our published results, we
now demonstrate how Rab32 can perform these many functions:
at the MAM, Rab32 determines the activity of dynamin-related
protein 1 (Drp1), the enzyme mediating mitochondria fission.
Moreover, Rab32 also directly interacts with this GTPase and is
therefore an upstream regulator of Drp1 and thus, mitochondrial
fission. Like Rab32, we demonstrate that other Rab32 family
proteins, but not other Rabs found on organelles of the late
secretory pathway, also have to be active to permit mitochondria
fission. Thus, Rab32 family proteins form a MAM-associated,
regulatory bridge between protein secretion and mitochondria.