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Published November 17, 2016 | Published + Supplemental Material
Journal Article Open

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

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.

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

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Supplemental Material - elife-17896-supp-v1.zip

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