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Elimination of paternal mitochondria in mouse embryos occurs through autophagic degradation dependent on PARKIN and MUL1

Rojansky, Rebecca and Cha, Moon-Yong and Chan, David C. (2016) Elimination of paternal mitochondria in mouse embryos occurs through autophagic degradation dependent on PARKIN and MUL1. eLife, 5 . Art. No. e17896. ISSN 2050-084X. PMCID PMC5127638. doi:10.7554/eLife.17896. https://resolver.caltech.edu/CaltechAUTHORS:20161121-101729796

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Abstract

A defining feature of mitochondria is their maternal mode of inheritance. However, little is understood about the cellular mechanism through which paternal mitochondria, delivered from sperm, are eliminated from early mammalian embryos. Autophagy has been implicated in nematodes, but whether this mechanism is conserved in mammals has been disputed. Here, we show that cultured mouse fibroblasts and pre-implantation embryos use a common pathway for elimination of mitochondria. Both situations utilize mitophagy, in which mitochondria are sequestered by autophagosomes and delivered to lysosomes for degradation. The E3 ubiquitin ligases PARKIN and MUL1 play redundant roles in elimination of paternal mitochondria. The process is associated with depolarization of paternal mitochondria and additionally requires the mitochondrial outer membrane protein FIS1, the autophagy adaptor P62, and PINK1 kinase. Our results indicate that strict maternal transmission of mitochondria relies on mitophagy and uncover a collaboration between MUL1 and PARKIN in this process.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.7554/eLife.17896DOIArticle
https://elifesciences.org/content/5/e17896PublisherArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5127638/PubMed CentralArticle
ORCID:
AuthorORCID
Chan, David C.0000-0002-0191-2154
Additional Information:© 2016, Rojansky et al. This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited. Received May 17, 2016. Accepted November 14, 2016. Published November 17, 2016. We are grateful to Shirley Pease (Director, Transgenic Core at Caltech) for training and advice on embryo injection. We thank Katherine Kim for preliminary work with MUL1 knockdown experiments, Kurt Reichermeier for advice on the ubiquitin assay, Ruohan Wang for technical assistance with p62 overexpression, and Hsiuchen Chen for advice on animal work. RR is supported by an NIH NIGMS training grant (GM08042) and the UCLA Medical Scientist Training Program. Funding: National Institute of General Medical Sciences - GM08042. National Institutes of Health - GM119388, GM083121. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. Author Contributions: RR, Conception and design, Acquisition of data, Analysis and interpretation of data, Drafting or revising the article; M-YC, Acquisition of data, Analysis and interpretation of data; DCC, Conception and design, Analysis and interpretation of data, Drafting or revising the article
Funders:
Funding AgencyGrant Number
NIHGM08042
UCLA Medical Scientist Training ProgramUNSPECIFIED
NIHGM119388
NIHGM083121
PubMed Central ID:PMC5127638
DOI:10.7554/eLife.17896
Record Number:CaltechAUTHORS:20161121-101729796
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20161121-101729796
Official Citation:Elimination of paternal mitochondria in mouse embryos occurs through autophagic degradation dependent on PARKIN and MUL1 Rebecca Rojansky Moon-Yong Cha David C Chan eLife 2016;5:e17896
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:72195
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:21 Nov 2016 18:23
Last Modified:11 Nov 2021 04:57

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