Program of the 2001 International Worm Meeting - Sternberg Lab ...

829
829. Search for novel proteins
affecting mitochondrial inner and
outer membrane division.
Ayako Hasegawa, Dan Rube,
Ashley Wright, Alexander van der
Bliek
Department of Biological Chemistry, UCLA,
Box 951737, Los Angeles CA
Mitochondria are dynamic structures that often
divide and fuse throughout the life of a cell.
Mitochondrial division is necessary to keep up
with cell growth and division and it is often also
necessary in response to changes in the cellular
environment. Mitochondrial division is a
complex process requiring coordination between
inner and outer membrane division. We have
previously shown that a dynamin-related
protein, called DRP-1, is required for division of
the mitochondrial outer membrane, but not for
division of the inner membrane (1). Although
we suspect that DRP-1 acts as part of a larger
protein complex, other factors controlling outer
membrane division in C. elegans are unknown,
nor are inner membrane factors known. In a
companion abstract by Rube et al. the possible
role of other endocytic components in
mitochondrial outer membrane division is
explored further. Here, we look for novel factors
that control outer and inner membrane division.
We are testing candidate proteins by injecting
antisense constructs under control of the myo-3
promoter, which is expressed at high levels in C.
elegans bodywall muscles, along with GFP
targeted to mitochondria. For the outer
membrane, we have started with some of the
known outer membrane proteins such as
components of the voltage dependent anion
channel (VDAC). One component of VDAC,
the peripheral benzodiazepine receptor (PBR), is
of special interest, because benzodiazepine has
been shown to induce mitochondrial division in
mammalian cells. We are currently testing the
possible role of C. elegans PBR in division,
using GFP-tags and antisense PBR under
control of the myo-3 promoter. We are also
exploring the possible roles of mitochondrial
matrix proteins in division. A large number of
novel matrix proteins were identified using a
bioinformatics approach (2). Our preliminary
results suggest that some of these affect division
of the mitochondrial inner membrane. These
results will be presented at the meeting.
1. Labrousse, A.M., M. Zapaterra, D.A. Rube,
and A.M. van der Bliek (1999) C. elegans
dynamin-related protein drp-1 controls severing
of the mitochondrial outer membrane, Mol. Cell
4, 815-826.
2. Marcotte, E.M., I. Xenarios, A.M. van Der
Bliek, and D. Eisenberg (2000) Localizing
proteins in the cell from their phylogenetic
profiles, Proc Natl Acad Sci U S A 97,
12115-12120.
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