PARENTAL MITOCHONDRIA ELIMINATION
Studying selective elimination of parental mitochondria during animal development
In most eukaryotes, the inheritance of mitochondrion and its DNA (mtDNA) is strictly maternal, despite the fact that a sperm can inject up to 100 functional mitochondria into the oocyte during fertilization. The mechanisms responsible for selective elimination of paternal mitochondria have been a major question in developmental biology. We initiated study of this fascinating process in C. elegans and developed a sensitive PCR-based assay and a microscopy assay to track the fate of paternal mitochondria in fertilized oocytes, starting from sperm entry into the oocyte to their eventual elimination. We found that the paternal mitochondrial elimination process (PME) is conserved in C. elegans and that the maternal autophagy/lysosomal pathway actively participates in this process (Zhou et al., Cell Research 2011). We have performed several RNAi screens and candidate-based screens to identify maternal and paternal factors important for paternal mitochondrial elimination and have identified multiple genes important for PME, including a mitochondrial nuclease, endonuclease G, that mediates paternal mitochondrial self-destruction after fertilization (Zhou et al., Science 2016) and two mitochondrial GTPases, DRP-1 and FZO-1, that act paternally and maternally, respectively, to regulate the kinetics and specificity of paternal mitochondrial elimination (Wang et al., Nature Communications 2016). Genetic, cell biological, and biochemical characterization of the identified genes will help reveal signals that mark sperm mitochondria for destruction and the signaling pathways that recognize the signals to activate the maternal degradation machineries. Understanding of these important questions will be critical for treating various inherited human mitochondrial disease and for determining the safety and efficiency of animal cloning involving spermatid or sperm microinjection.
Zhou, Q.H., Li, H.M., and Xue, D. (2011). Elimination of Paternal mitochondria through the lysosomal degradation pathway in C. elegans.Cell Research 21, 1662-1669 (Abstract and PDF).
Zhou, Q.H.*, Li, H.M.*, Li, H.Z.*, Nakagawa, A., Harry, B., Lee, E.S., Lin, J., William, D., Mitani, S., Yuan, H., Kang, B.H.#, and Xue, D.# (2016). Mitochondrial endonuclease G mediates breakdown of paternal mitochondria following fertilization. Science 353, 394-399 (Abstract and PDF). *Equal contribution. #Co-corresponding authors. Science Perspectives, Nature Reviews Molecular Cell Biology, The New York Times, ScienceNews, TheScientist, Le Scienze, MedicalXpress, Sciences et Avenir, DAGENS Medicin, 新华网, ScienceAlert, Bionews, THE WIRE, and THE VERGE.
Wang, Y.*, Zhang, Y.*, Chen, L.W., Liang, Q., Yin, X.M., Miao, L., Kang, B.H.#, and Xue, D.# (2016). Kinetics and specificity of paternal mitochondrial elimination in Caenorhabditis elegans. Nature Communications 7, 12569. DOI: 10.1038/ncomms12569. (Abstract and PDF). *Equal contribution. #Co-corresponding authors.