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Fis1, Mff, MiD49 and MiD51 facilitate Drp1 recruitment for mitochondrial fission

Losón, Oliver Calvin and Chen, Hsiuchen and Chan, David C. (2013) Fis1, Mff, MiD49 and MiD51 facilitate Drp1 recruitment for mitochondrial fission. FASEB Journal, 27 . Art. No. 582.2. ISSN 0892-6638. https://resolver.caltech.edu/CaltechAUTHORS:20130711-101356451

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Abstract

Several mitochondrial outer membrane proteins—Fis1, Mff, MiD49, and MiD51—have been proposed to promote mitochondrial fission by recruiting the cytosolic GTPase Drp1, but fundamental issues remain concerning their function. A recent study supported such a role for Mff, but not for Fis1. In addition, it is unclear whether MiD49 and MiD51 activate or inhibit fission because their overexpression causes extensive mitochondrial elongation. It is also unknown whether these proteins can act in the absence of one another to mediate fission. Using Fis1-null, Mff null, and Fis1/Mff -null cells, we show that both Fis1 and Mff have roles in mitochondrial fission. We employ several independent, quantitative techniques to show that these cell lines have significantly different mitochondrial elongation phenotypes. Using a specialized image analysis technique, we find that Fis1 and Mff are important for regulating the number and size of Drp1 fluorescent puncta on mitochondria. Finally, we find that either MiD49 or MiD51 can mediate Drp1 recruitment and mitochondrial fission in the absence of Fis1 and Mff. We also demonstrate that a significant enhancement of Drp1 phosphorylation at S637 is causal for the elongation phenotype during MiD overexpression. These results demonstrate that multiple receptors can recruit Drp1 to mediate mitochondrial fission, and suggest that these proteins may function in parallel pathways.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://www.fasebj.org/cgi/content/meeting_abstract/27/1_MeetingAbstracts/582.2PublisherArticle
ORCID:
AuthorORCID
Chan, David C.0000-0002-0191-2154
Additional Information:© 2013 FASEB. This work was supported by the National Institutes of Health (GM062967). OCL was supported by a R. L. Kirschstein National Research Service Award (5F31GM089327).
Funders:
Funding AgencyGrant Number
NIHGM062967
NIH Predoctoral Fellowship5F31GM089327
Record Number:CaltechAUTHORS:20130711-101356451
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20130711-101356451
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:39309
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:11 Jul 2013 18:01
Last Modified:24 Feb 2020 10:30

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