Journal article
Receptor-mediated Drp1 oligomerization on endoplasmic reticulum
The Journal of cell biology, Vol.216(12), pp.4123-4139
12/04/2017
DOI: 10.1083/jcb.201610057
PMCID: PMC5716263
PMID: 29158231
Abstract
Drp1 is a dynamin guanosine triphosphatase important for mitochondrial and peroxisomal division. Drp1 oligomerization and mitochondrial recruitment are regulated by multiple factors, including interaction with mitochondrial receptors such as Mff, MiD49, MiD51, and Fis. In addition, both endoplasmic reticulum (ER) and actin filaments play positive roles in mitochondrial division, but mechanisms for their roles are poorly defined. Here, we find that a population of Drp1 oligomers is associated with ER in mammalian cells and is distinct from mitochondrial or peroxisomal Drp1 populations. Subpopulations of Mff and Fis1, which are tail-anchored proteins, also localize to ER. Drp1 oligomers assemble on ER, from which they can transfer to mitochondria. Suppression of Mff or inhibition of actin polymerization through the formin INF2 significantly reduces all Drp1 oligomer populations (mitochondrial, peroxisomal, and ER bound) and mitochondrial division, whereas Mff targeting to ER has a stimulatory effect on division. Our results suggest that ER can function as a platform for Drp1 oligomerization, and that ER-associated Drp1 contributes to mitochondrial division.
Details
- Title: Subtitle
- Receptor-mediated Drp1 oligomerization on endoplasmic reticulum
- Creators
- Wei-Ke Ji - Department of Biochemistry and Molecular Biology, School of Basic Medicine and the Collaborative Innovation Center for Brain Science, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaRajarshi Chakrabarti - Department of Biochemistry and Cell Biology, Geisel School of Medicine at Dartmouth, Hanover, NHXintao Fan - Department of Biochemistry and Cell Biology, Geisel School of Medicine at Dartmouth, Hanover, NHLori Schoenfeld - Department of Biochemistry and Cell Biology, Geisel School of Medicine at Dartmouth, Hanover, NHStefan Strack - Department of Pharmacology, Carver School of Medicine, University of Iowa, Iowa City, IAHenry N Higgs - Department of Biochemistry and Cell Biology, Geisel School of Medicine at Dartmouth, Hanover, NH henry.higgs@dartmouth.edu
- Resource Type
- Journal article
- Publication Details
- The Journal of cell biology, Vol.216(12), pp.4123-4139
- Publisher
- United States
- DOI
- 10.1083/jcb.201610057
- PMID
- 29158231
- PMCID
- PMC5716263
- ISSN
- 0021-9525
- eISSN
- 1540-8140
- Grant note
- S10 OD010330 / NIH HHS R56 NS056244 / NINDS NIH HHS R21 NS087908 / NINDS NIH HHS P20 GM113132 / NIGMS NIH HHS R01 GM106000 / NIGMS NIH HHS R35 GM122545 / NIGMS NIH HHS R01 GM069818 / NIGMS NIH HHS R01 NS056244 / NINDS NIH HHS
- Language
- English
- Date published
- 12/04/2017
- Academic Unit
- Pathology; Iowa Neuroscience Institute; Neuroscience and Pharmacology
- Record Identifier
- 9984040255202771
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