Unraveling the mechanism of ER-­associated organelle constriction and division

NIH RePORTER · NIH · R01 · $250,335 · view on reporter.nih.gov ↗

Abstract

SUMMARY The ER has an elaborate structure. It consists of a continuous network of membrane sheets and tubules that spread like a spiderweb into every corner of the cytoplasm. Structural domains of the ER have been attributed different functions. ER sheets are studded with ribosomes and are the preferred location for the translation, translocation, and folding of membrane and lumenal proteins. However, very little is known about the function significance of ER tubules even though they account for at least half of the surface area of the ER in most eukaryotic cells. My lab has uncovered a surprising new function for ER tubules in regulating the biogenesis of endosomes and mitochondria at membrane contact sites. We discovered that ER membrane contact sites define the position where mitochondria and early and late endosomes undergo constriction and then division (1, 2). On mitochondria, ER contact is purposefully localized to the position of nucleoid segration, division machinery recruitment, initial constriction, and through fission. On endosomes, ER tubules are recruited to cargo sorting domains that constrict and undergo fission. Our current research goals are to understand how ER contact sites are regulated and purposefully positioned and to discover by what mechanism can ER contact drive the constriction and fission of other organelles. These studies are novel and are aimed at unraveling the factors, functions, and mechanism of ER-mediated organelle division. 1) Friedman JR, Lackner LL, West M, DiBenedetto JR, Nunnari J & Voeltz GK* (2011). ER Tubules Mark Sites of Mitochondrial Division. Science 334: 358-362. 2) Rowland AA, Chitwood P, Phillips MJ & Voeltz GK* (2014) ER contact sites define the position and timing of endosome fission. Cell 159: 1027-41.

Key facts

NIH application ID
9848597
Project number
5R01GM120998-04
Recipient
UNIVERSITY OF COLORADO
Principal Investigator
Gia Voeltz
Activity code
R01
Funding institute
NIH
Fiscal year
2020
Award amount
$250,335
Award type
5
Project period
2017-01-01 → 2021-12-31