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.

Public Health Relevance

The Endoplasmic Reticulum (ER) forms membrane contact sites (MCSs) with multiple other organelles. My lab has discovered a new function for ER MCSs in defining the position where both mitochondria and early and late endosomes undergo constriction and then division. Our current research goals are to understand how ER contact sites are recruited, regulated, and purposefully positioned to drive the constriction and fission of other organelles.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM120998-03
Application #
9613833
Study Section
Nuclear and Cytoplasmic Structure/Function and Dynamics Study Section (NCSD)
Program Officer
Flicker, Paula F
Project Start
2017-01-01
Project End
2020-12-31
Budget Start
2019-01-01
Budget End
2019-12-31
Support Year
3
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of Colorado at Boulder
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
007431505
City
Boulder
State
CO
Country
United States
Zip Code
80303
Hoyer, Melissa J; Chitwood, Patrick J; Ebmeier, Christopher C et al. (2018) A Novel Class of ER Membrane Proteins Regulates ER-Associated Endosome Fission. Cell 175:254-265.e14