title: Mitochondrial endonuclease G mediates breakdown of paternal mitochondria upon fertilization.
abstract: Mitochondria are inherited maternally in most animals, but the mechanisms of selective paternal mitochondrial elimination (PME) are unknown. While examining fertilization in Caenorhabditis elegans, we observed that paternal mitochondria rapidly lose their inner membrane integrity. CPS-6, a mitochondrial endonuclease G, serves as a paternal mitochondrial factor that is critical for PME. We found that CPS-6 relocates from the intermembrane space of paternal mitochondria to the matrix after fertilization to degrade mitochondrial DNA. It acts with maternal autophagy and proteasome machineries to promote PME. Loss of cps-6 delays breakdown of mitochondrial inner membranes, autophagosome enclosure of paternal mitochondria, and PME. Delayed removal of paternal mitochondria causes increased embryonic lethality, demonstrating that PME is important for normal animal development. Thus, CPS-6 functions as a paternal mitochondrial degradation factor during animal development.
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA.
authors.forename: Haimin
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA. Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309, USA.
authors.forename: Hanzeng
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA.
authors.forename: Akihisa
authors.initials: A
authors.lastname: Nakagawa
authors.affiliation: Institute of Molecular Biology, Academia Sinica, Taipei 11529, Taiwan.
authors.forename: Jason L J
authors.initials: JL
authors.lastname: Lin
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA.
authors.forename: Eui-Seung
authors.initials: ES
authors.lastname: Lee
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA. Medical Scientist Training Program, University of Colorado, Aurora, CO 80045, USA.
authors.forename: Brian L
authors.initials: BL
authors.lastname: Harry
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA.
authors.forename: Riley Robert
authors.initials: RR
authors.lastname: Skeen-Gaar
authors.affiliation: Department of Physiology, Tokyo Women's Medical University, School of Medicine and CREST, Japan Science and Technology Agency, Tokyo 162-8666, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Suehiro
authors.affiliation: Department of Microbiology and Cell Science, University of Florida, Gainesville, FL 32611, USA.
authors.forename: Donna
authors.initials: D
authors.lastname: William
authors.affiliation: Department of Physiology, Tokyo Women's Medical University, School of Medicine and CREST, Japan Science and Technology Agency, Tokyo 162-8666, Japan.
authors.forename: Shohei
authors.initials: S
authors.lastname: Mitani
authors.affiliation: Institute of Molecular Biology, Academia Sinica, Taipei 11529, Taiwan.
authors.forename: Hanna S
authors.initials: HS
authors.lastname: Yuan
authors.affiliation: School of Life Sciences, Centre for Cell and Developmental Biology and State Key Laboratory of Agrobiotechnology, Chinese University of Hong Kong, Hong Kong, China. ding.xue@colorado.edu bkang@cuhk.edu.hk.
authors.forename: Byung-Ho
authors.initials: BH
authors.lastname: Kang
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA. ding.xue@colorado.edu bkang@cuhk.edu.hk.
authors.forename: Ding
authors.initials: D
authors.lastname: Xue
mesh_terms: D000818:Animals; D001343:Autophagy; D017173:Caenorhabditis elegans / Q000196:embryology* / Q000201:enzymology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D004272:DNA, Mitochondrial / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000201:enzymology; D004706:Endodeoxyribonucleases / Q000235:genetics / Q000378:metabolism*; D005306:Fertilization; D008297:Male; D008928:Mitochondria / Q000201:enzymology*; D051336:Mitochondrial Membranes / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D013094:Spermatozoa / Q000201:enzymology / Q000648:ultrastructure
chemical_list: D029742:Caenorhabditis elegans Proteins; C469544:Cps-6 protein, C elegans; D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins; D004706:Endodeoxyribonucleases; C052391:endonuclease G; D046988:Proteasome Endopeptidase Complex