Receptor-mediated Drp1 oligomerization on endoplasmic reticulum
| Autor: | Wei-Ke Ji, Lori W. Schoenfeld, Henry N. Higgs, Stefan Strack, Rajarshi Chakrabarti, Xintao Fan |
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| Rok vydání: | 2017 |
| Předmět: |
Dynamins
0301 basic medicine FIS1 endocrine system Population Formins Mitochondrion Endoplasmic Reticulum Mitochondrial Dynamics Article GTP Phosphohydrolases Mitochondrial Proteins 03 medical and health sciences 0302 clinical medicine Cell Line Tumor Humans RNA Small Interfering education Research Articles Actin Dynamin 030304 developmental biology 0303 health sciences education.field_of_study Osteoblasts biology Endoplasmic reticulum Microfilament Proteins Membrane Proteins Cell Biology Peroxisome Peptide Elongation Factors Mitochondria Cell biology INF2 030104 developmental biology Gene Expression Regulation biology.protein Protein Multimerization Microtubule-Associated Proteins 030217 neurology & neurosurgery |
| Zdroj: | The Journal of Cell Biology |
| Popis: | Assembly of the dynamin GTPase Drp1 into constriction-competent oligomers is a key event in mitochondrial division. Here, Ji et al. show that Drp1 oligomerization can occur on endoplasmic reticulum through an ER-bound population of the tail-anchored protein Mff. 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. |
| Databáze: | OpenAIRE |
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