Skip to main content Accessibility help
×
Home
Hostname: page-component-5959bf8d4d-67wr7 Total loading time: 0.241 Render date: 2022-12-09T06:22:45.352Z Has data issue: true Feature Flags: { "useRatesEcommerce": false } hasContentIssue true

Article contents

Autophagy and ubiquitin-mediated proteolysis may not be involved in the degradation of spermatozoon mitochondria in mouse and porcine early embryos

Published online by Cambridge University Press:  16 December 2014

Yong-Xun Jin
Affiliation:
Chungbuk National University, Department of Animal Science, Cheongju, Chungbuk, South Korea.
Zhong Zheng
Affiliation:
Chungbuk National University, Department of Veterinary, Cheongju, Chungbuk, South Korea.
Xian-Feng Yu
Affiliation:
College of Animal Science, Jilin University, Changchun 130062, China.
Jia-Bao Zhang
Affiliation:
College of Animal Science, Jilin University, Changchun 130062, China.
Suk Namgoong
Affiliation:
Chungbuk National University, Department of Animal Science, Cheongju, Chungbuk, South Korea.
Xiang-Shun Cui
Affiliation:
Chungbuk National University, Department of Animal Science, Cheongju, Chungbuk, South Korea.
Sang-Hwan Hyun
Affiliation:
Chungbuk National University, Department of Veterinary, Cheongju, Chungbuk, South Korea.
Nam-Hyung Kim*
Affiliation:
Chungbuk National University, Department of Animal Science, Cheongju, Chungbuk, South Korea.
*
All correspondence to: Nam-Hyung Kim. Chungbuk National University, Department of Animal Science, Cheongju, Chungbuk, South Korea. e-mail: nhkim@chungbuk.ac.kr

Summary

The mitochondrial genome is maternally inherited in animals, despite the fact that paternal mitochondria enter oocytes during fertilization. Autophagy and ubiquitin-mediated degradation are responsible for the elimination of paternal mitochondria in Caenorhabditis elegans; however, the involvement of these two processes in the degradation of paternal mitochondria in mammals is not well understood. We investigated the localization patterns of light chain 3 (LC3) and ubiquitin in mouse and porcine embryos during preimplantation development. We found that LC3 and ubiquitin localized to the spermatozoon midpiece at 3 h post-fertilization, and that both proteins were colocalized with paternal mitochondria and removed upon fertilization during the 4-cell stage in mouse and the zygote stage in porcine embryos. Sporadic paternal mitochondria were present beyond the morula stage in the mouse, and paternal mitochondria were restricted to one blastomere of 4-cell embryos. An autophagy inhibitor, 3-methyladenine (3-MA), did not affect the distribution of paternal mitochondria compared with the positive control, while an autophagy inducer, rapamycin, accelerated the removal of paternal mitochondria compared with the control. After the intracytoplasmic injection of intact spermatozoon into mouse oocytes, LC3 and ubiquitin localized to the spermatozoon midpiece, but remnants of undegraded paternal mitochondria were retained until the blastocyst stage. Our results show that paternal mitochondria colocalize with autophagy receptors and ubiquitin and are removed after in vitro fertilization, but some remnants of sperm mitochondrial sheath may persist up to morula stage after intracytoplasmic spermatozoon injection (ICSI).

Type
Research Article
Copyright
Copyright © Cambridge University Press 2014 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Aitken, R.J. (1995). Free radicals, lipid peroxidation and spermatozoon function. Reprod. Fertil. Dev. 7, 659–68.CrossRefGoogle Scholar
Al Rawi, S., Louvet-Vallee, S., Djeddi, A., Sachse, M., Culetto, E., Hajjar, C., Boyd, L., Legouis, R. & Galy, V. (2011). Postfertilization autophagy of spermatozoon organelles prevents paternal mitochondrial DNA transmission. Science 334, 1144–7.CrossRefGoogle ScholarPubMed
Ankel-Simons, F. & Cummins, J.M. (1996). Misconceptions about mitochondria and mammalian fertilization: implications for theories on human evolution. Proc. Natl. Acad. Sci. USA 93, 13859–63.CrossRefGoogle Scholar
Birky, C.W., Jr. (2001). The inheritance of genes in mitochondria and chloroplasts: laws, mechanisms, and models. Annu. Rev. Genet. 35, 125–48.CrossRefGoogle ScholarPubMed
Blommaart, E.F., Luiken, J.J., Blommaart, P.J., van Woerkom, G.M. & Meijer, A.J. (1995). Phosphorylation of ribosomal protein S6 is inhibitory for autophagy in isolated rat hepatocytes. J. Biol. Chem., 270, 2320–6.CrossRefGoogle ScholarPubMed
Cummins, J.M., Wakayama, T. & Yanagimachi, R. (1997). Fate of microinjected spermatozoon components in the mouse oocyte and embryo. Zygote 5, 301–8.CrossRefGoogle ScholarPubMed
Gyllensten, U., Wharton, D., Josefsson, A. & Wilson, A.C. (1991). Paternal inheritance of mitochondrial DNA in mice. Nature 352, 255–7.CrossRefGoogle ScholarPubMed
Hecht, N.B., Liem, H., Kleene, K.C., Distel, R.J. & Ho, S.M. (1984). Maternal inheritance of the mouse mitochondrial genome is not mediated by a loss or gross alteration of the paternal mitochondrial DNA or by methylation of the oocyte mitochondrial DNA. Dev. Biol. 102, 452–61.CrossRefGoogle ScholarPubMed
Hiraoka, J. & Hirao, Y. (1988). Fate of spermatozoon tail components after incorporation into the hamster egg. Gamete Res. 19, 369–80.CrossRefGoogle ScholarPubMed
Houshmand, M., Holme, E., Hanson, C., Wennerholm, U.B. & Hamberger, L. (1997). Is paternal mitochondrial DNA transferred to the offspring following intracytoplasmic spermatozoon injection. J. Assist. Reprod. Genet. 14, 223–7.CrossRefGoogle ScholarPubMed
Jansen, R.P. & de Boer, K. (1998). The bottleneck: mitochondrial imperatives in oogenesis and ovarian follicular fate. Mol. Cell. Endocrinol. 145, 81–8.CrossRefGoogle ScholarPubMed
Jin, Y.X., Cui, X.S., Yu, X.F., Lee, S.H., Wang, Q.L., Gao, W.W., Xu, Y.N., Sun, S.C., Kong, I.K. & Kim, N.H. (2012). Cat fertilization by mouse spermatozoon injection. Zygote 20, 371–8.CrossRefGoogle ScholarPubMed
Kamada, Y., Funakoshi, T., Shintani, T., Nagano, K., Ohsumi, M. & Ohsumi, Y. (2000). Tor-mediated induction of autophagy via an Apg1 protein kinase complex. J. Cell Biol. 150, 1507–13.CrossRefGoogle ScholarPubMed
Kaneda, H., Hayashi, J., Takahama, S., Taya, C., Lindahl, K.F. & Yonekawa, H. (1995). Elimination of paternal mitochondrial DNA in intraspecific crosses during early mouse embryogenesis. Proc. Natl. Acad. Sci. USA 92, 4542–6.CrossRefGoogle ScholarPubMed
Kraft, C., Peter, M. & Hofmann, K. (2010). Selective autophagy: ubiquitin-mediated recognition and beyond. Nat. Cell. Biol. 12, 836–41.CrossRefGoogle ScholarPubMed
Luo, S.M. & Sun, Q.Y. (2013). Autophagy is not involved in the degradation of spermatozoon mitochondria after fertilization in mice. Autophagy 9, 2156–7.CrossRefGoogle ScholarPubMed
Luo, S.M., Ge, Z.J., Wang, Z.W., Jiang, Z.Z., Wang, Z.B., Ouyang, Y.C., Hou, Y., Schatten, H. & Sun, Q.Y. (2013). Unique insights into maternal mitochondrial inheritance in mice. Proc. Natl. Acad. Sci. USA 110, 13038–43.CrossRefGoogle ScholarPubMed
Nishida, Y., Arakara, T., Fujitani, K., Yamaguchi, H., Mizuta, H., Kanaseki, T., Komatsu, M., Otsu, K., Tsujimoto, Y. & Shimizu, S. (2009). Discovery of Atg5/Atg7-independent alternative macroautophagy. Nature 461, 654–8.CrossRefGoogle ScholarPubMed
Nishimura, Y., Yoshinari, T., Naruse, K., Yamada, T., Sumi, K., Mitani, H., Higashiyama, T. & Kuroiwa, T. (2006). Active digestion of spermatozoon mitochondrial DNA in single living spermatozoon revealed by optical tweezers. Proc. Natl. Acad. Sci. USA 103, 1382–7.CrossRefGoogle ScholarPubMed
Noda, T. & Ohsumi, Y. (1998). Tor, a phosphatidylinositol kinase homologue, controls autophagy in yeast. J. Biol. Chem. 273, 3963–6.CrossRefGoogle Scholar
Politi, Y., Gal, L., Kalifa, Y., Ravid, L., Elazar, Z. & Arama, E. (2014). Paternal mitochondrial destruction after fertilization is mediated by a common endocytic and autophagic pathway in Drosophila . Dev. Cell 29, 305–20.CrossRefGoogle ScholarPubMed
Rusten, T.E., Lindmo, K., Juhasz, G., Sass, M., Seglen, P.O., Brech, A. & Stenmark, H. (2004). Programmed autophagy in the Drosophila fat body is induced by ecdysone through regulation of the PI3K pathway. Dev. Cell 7, 179–92.CrossRefGoogle ScholarPubMed
Sato, M. & Sato, K. (2011). Degradation of paternal mitochondria by fertilization-triggered autophagy in C. elegans embryos. Science 334, 1141–4.CrossRefGoogle Scholar
Sato, M. & Sato, K. (2013). Maternal inheritance of mitochondrial DNA by diverse mechanisms to eliminate paternal mitochondrial DNA. Biochim. Biophys. Acta 1833, 1979–84.CrossRefGoogle ScholarPubMed
Shalgi, R., Magnus, A., Jones, R. & Phillips, D.M. (1994). Fate of spermatozoon organelles during early embryogenesis in the rat. Mol. Reprod. Dev. 37, 264–71.CrossRefGoogle Scholar
Sheng, Y., Sun, B., Guo, W.T., Zhang, Y.H., Liu, X., Xing, Y. & Dong, D.L. (2013). 3-Methyladenine induces cell death and its interaction with chemotherapeutic drugs is independent of autophagy. Biochem. Biophys. Res. Commun. 432, 59.CrossRefGoogle Scholar
Song, W.H., Ballard, J.W., Yi, Y.J. & Sutovsky, P. (2014). Regulation of mitochondrial genome inheritance by autophagy and ubiquitin-proteasome system: implications for health, fitness, and fertility. Biomed. Res. Int. 2014, 981867.CrossRefGoogle ScholarPubMed
Sun, S.C., Xu, Y.N., Li, Y.H., Lee, S.E., Jin, Y.X., Cui, X.S. & Kim, N.H. (2011). WAVE2 regulates meiotic spindle stability, peripheral positioning and polar body emission in mouse oocytes. Cell Cycle 10, 1853–60.CrossRefGoogle ScholarPubMed
Sun, S.C., Gao, W.W., Xu, Y.N., Jin, Y.X., Wang, Q.L., Yin, X.J., Cui, X.S. & Kim, N.H. (2012). Degradation of actin nucleators affects cortical polarity of aged mouse oocytes. Fertil. Steril. 97, 984–90.CrossRefGoogle ScholarPubMed
Sutovsky, P., Hewitson, L., Simerly, C.R., Tengowski, M.W., Navara, C.S., Haavisto, A. & Schatten, G. (1996a). Intracytoplasmic spermatozoon injection for Rhesus monkey fertilization results in unusual chromatin, cytoskeletal, and membrane events, but eventually leads to pronuclear development and spermatozoon aster assembly. Hum. Reprod. 11, 1703–12.CrossRefGoogle ScholarPubMed
Sutovsky, P., Navara, C.S. & Schatten, G. (1996b). Fate of the spermatozoon mitochondria, and the incorporation, conversion, and disassembly of the spermatozoon tail structures during bovine fertilization. Biol. Reprod. 55, 1195–205.CrossRefGoogle ScholarPubMed
Sutovsky, P., Moreno, R.D., Ramalho-Santos, J., Dominko, T., Simerly, C. & Schatten, G. (1999). Ubiquitin tag for spermatozoon mitochondria. Nature 402, 371–2.Google Scholar
Sutovsky, P., Moreno, R.D., Ramalho-Santos, J., Dominko, T., Simerly, C. & Schatten, G (2000). Ubiquitinated spermatozoon mitochondria, selective proteolysis, and the regulation of mitochondrial inheritance in mammalian embryos. Biol. Reprod. 63, 583–90.CrossRefGoogle ScholarPubMed
Sutovsky, P., McCauley, T.C., Sutovsky, M. & Day, B.N. (2003). Early degradation of paternal mitochondria in domestic pig (Sus scrofa) is prevented by selective proteasomal inhibitors lactacystin and MG132. Biol. Reprod. 68, 1793–800.CrossRefGoogle ScholarPubMed
Szollosi, D. (1965). The fate of spermatozoon middle-piece mitochondria in the rat egg. J. Exp. Zool. 159, 367–77.CrossRefGoogle ScholarPubMed
Takatsuka, C., Inoue, Y., Matsuoka, K. & Moriyasu, Y. (2004). 3-Methyladenine inhibits autophagy in tobacco culture cells under sucrose starvation conditions. Plant Cell Physiol. 45, 265–74.CrossRefGoogle ScholarPubMed
Tesarik, J., Rienzi, L., Ubaldi, F., Mendoza, C. & Greco, E. (2002). Use of a modified intracytoplasmic spermatozoon injection technique to overcome spermatozoon-borne and oocyte-borne oocyte activation failures. Fertil. Steril. 78, 619–24.CrossRefGoogle ScholarPubMed
Torroni, A., D’Urbano, L., Rengo, C., Scozzari, R., Sbracia, M., Manna, C., Cavazzini, C. & Sellitto, D. (1998). Intracytoplasmic injection of spermatozoa does not appear to alter the mode of mitochondrial DNA inheritance. Hum. Reprod. 13, 1747–9.CrossRefGoogle Scholar
Yorimitsu, T., Klionsky, D.J. (2005). Autophagy: molecular machinery for self-eating. Cell Death Diff. 12, 1542–52.CrossRefGoogle ScholarPubMed
Wang, K. & Klionsky, D.J (2011). Mitochondria removal by autophagy. Autophagy 7, 297300.CrossRefGoogle ScholarPubMed
Zheng, Z., Jia, J.L., Bou, G., Hu, L.L., Wang, Z.D., Shen, X.H., Shan, Z.Y., Shen, J.L., Liu, Z.H. & Lei, L. (2012). rRNA genes are not fully activated in mouse somatic cell nuclear transfer embryos. J. Biol. Chem. 287, 19949–60.CrossRefGoogle Scholar
Zhou, Q., Li, H. & Xue, D. (2011). Elimination of paternal mitochondria through the lysosomal degradation pathway in C. elegans . Cell Res. 21, 1662–9.CrossRefGoogle ScholarPubMed
6
Cited by

Save article to Kindle

To save this article to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Autophagy and ubiquitin-mediated proteolysis may not be involved in the degradation of spermatozoon mitochondria in mouse and porcine early embryos
Available formats
×

Save article to Dropbox

To save this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you used this feature, you will be asked to authorise Cambridge Core to connect with your Dropbox account. Find out more about saving content to Dropbox.

Autophagy and ubiquitin-mediated proteolysis may not be involved in the degradation of spermatozoon mitochondria in mouse and porcine early embryos
Available formats
×

Save article to Google Drive

To save this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you used this feature, you will be asked to authorise Cambridge Core to connect with your Google Drive account. Find out more about saving content to Google Drive.

Autophagy and ubiquitin-mediated proteolysis may not be involved in the degradation of spermatozoon mitochondria in mouse and porcine early embryos
Available formats
×
×

Reply to: Submit a response

Please enter your response.

Your details

Please enter a valid email address.

Conflicting interests

Do you have any conflicting interests? *