SBF-SEM to assess nucleus-mitochondria contact sites and associated asynthetic fission in zebrafish skin

Session

Poster Session One

Authors

Ms Dhani Tracey-White (1), Dr Matthew Hayes (1)

Affiliations

1. UCL Institute of Ophthalmology

Keywords

SBF-SEM, TEM, nucleus-mitochondria, membrane contact site, contact site, asynthetic fission, Danio rerio, epidermis, site of membrane contact, corneocyte, keratocyte

Abstract text

The rapid increase in body surface area of growing zebrafish larvae (Danio rario) is partially accomplished by asynthetic fission of secondary epithelial cells (SECs) of the skin (Chan et al., 2022). There are two cycles of this atypical form of cell division which is unaccompanied by DNA replication; resulting in cells with a variable DNA content. Here, serial block face electron microscopy (SBF-SEM) and transmission electron microscopy of basal epithelium cells (that give rise to these SECs in zebrafish larvae) shows aggregation of mitochondria around the nucleus and the formation of nucleus-mitochondria membrane contact sites . Membrane aggregates appear in the lumen of the nuclear envelope at these sites of membrane contact in some cells, suggesting lipid turnover at the site. As the epithelial cells mature and stratify, the mitochondria are engulphed by extensions arising from the nuclear envelope. The mitochondrial outer membrane fragments and mitochondria fuse with the nuclear envelope and parts of the endoplasmic reticulum. Other organelles, including mitochondria and the Golgi apparatus, progressively localise to a central region of the cell and lose their integrity. Thus, asynthetic fission is accompanied by an atypical pattern of organelle destruction and a prelude to this is the formation of nucleus-mitochondria membrane contact sites.

References

Aoyama-Ishiwatari S and Hirabayashi Y (2021) Endoplasmic Reticulum–Mitochondria Contact Sites—Emerging Intracellular Signaling Hubs. Frontiers in Cell and Developmental Biology 9(May). DOI: 10.3389/fcell.2021.653828.

Chan KY, Yan CCS, Roan HY, et al. (2022) Skin cells undergo asynthetic fission to expand body surfaces in zebrafish. Nature 605(7908). Springer US: 119–125. DOI: 10.1038/s41586-022-04641-0.

Chen CH, Puliafito A, Cox BD, et al. (2016) Multicolor Cell Barcoding Technology for Long-Term Surveillance of Epithelial Regeneration in Zebrafish. Developmental Cell 36(6). Elsevier Inc.: 668–680. DOI: 10.1016/j.devcel.2016.02.017.

Csordás G, Weaver D and Hajnóczky G (2018) Endoplasmic Reticulum–Mitochondrial Contactology: Structure and Signaling Functions. Trends in Cell Biology 28(7). Elsevier Ltd: 523–540. DOI: 10.1016/j.tcb.2018.02.009.

Desai R, East DA, Hardy L, et al. (2020) Mitochondria form contact sites with the nucleus to couple prosurvival retrograde response. Science Advances 6(51): 1–16. DOI: 10.1126/SCIADV.ABC9955.

Eckhart L, Lippens S, Tschachler E, et al. (2013) Cell death by cornification. Biochimica et Biophysica Acta - Molecular Cell Research 1833(12): 3471–3480. DOI: 10.1016/j.bbamcr.2013.06.010.

Eisenberg-Bord M, Zung N, Collado J, et al. (2021) CNM1 mediates nucleus–mitochondria contact site formation in response to phospholipid levels. Journal of Cell Biology 220(11). DOI: 10.1083/jcb.202104100.

Elbaz Y and Schuldiner M (2011) Staying in touch: The molecular era of organelle contact sites. Trends in Biochemical Sciences 36(11). Elsevier Ltd: 616–623. DOI: 10.1016/j.tibs.2011.08.004.

Gatta AT and Levine TP (2017) Piecing Together the Patchwork of Contact Sites. Trends in Cell Biology 27(3). Elsevier Ltd: 214–229. DOI: 10.1016/j.tcb.2016.08.010.

Grunstein M (1997) Histone acetylation in chromatin structure and transcription. Nature 389(6649): 349–352. DOI: 10.1038/38664.

Hamasaki M, Furuta N, Matsuda A, et al. (2013) Autophagosomes form at ER-mitochondria contact sites. Nature 495(7441). Nature Publishing Group: 389–393. DOI: 10.1038/nature11910.

Kimmel CB, Ballard WW, Kimmel SR, et al. (1995) Stages of embryonic development of the zebrafish. Developmental Dynamics 203(3): 253–310. DOI: 10.1002/aja.1002030302.

Lavker RM and Gedeon Matoltsy A (1970) Formation of horny cells: The fate of cell organelles and differentiation products in ruminal epithelium. Journal of Cell Biology 44(3): 501–512. DOI: 10.1083/jcb.44.3.501.

Lechler T and Fuchs E (2005) Asymmetric cell divisions promote stratification and differentiation of mammalian skin. Nature 437(7056): 275–280. DOI: 10.1038/nature03922.

Li Q, Frank M, Thisse CI, et al. (2011) Zebrafish: A model system to study heritable skin diseases. Journal of Investigative Dermatology 131(3). Elsevier Masson SAS: 565–571. DOI: 10.1038/jid.2010.388.

Matsui T, Kadono-Maekubo N, Suzuki Y, et al. (2021) A unique mode of keratinocyte death requires intracellular acidification. Proceedings of the National Academy of Sciences of the United States of America 118(17): 1–10. DOI: 10.1073/pnas.2020722118.

Mehrel T, Hohl D, Rothnagel JA, et al. (1990) Identification of a major keratinocyte cell envelope protein, loricrin. Cell 61(6): 1103–1112. DOI: 10.1016/0092-8674(90)90073-N.

Prinz WA, Toulmay A and Balla T (2020) The functional universe of membrane contact sites. Nature Reviews Molecular Cell Biology 21(1). Springer US: 7–24. DOI: 10.1038/s41580-019-0180-9.

Quilhac A and Sire JY (1999) Spreading, proliferation, and differentiation of the epidermis after wounding a cichlid fish, Hemichromis bimaculatus. Anatomical Record 254(3): 435–451. DOI: 10.1002/(SICI)1097-0185(19990301)254:3<435::AID-AR15>3.0.CO;2-D.

Reinisch KM and Prinz WA (2021) Mechanisms of nonvesicular lipid transport. Journal of Cell Biology 220(3): 1–11. DOI: 10.1083/JCB.202012058.

Vecellio Reane D, Rizzuto R and Raffaello A (2020) The ER-mitochondria tether at the hub of Ca2+ signaling. Current Opinion in Physiology 17. Elsevier Ltd: 261–268. DOI: 10.1016/j.cophys.2020.08.013.

Wu H, Carvalho P and Voeltz GK (2018) Here, there, and everywhere: The importance of ER membrane contact sites. Science 361(6401). DOI: 10.1126/science.aan5835.

Zervopoulos SD, Boukouris AE, Saleme B, et al. (2022) MFN2-driven mitochondria-to-nucleus tethering allows a non-canonical nuclear entry pathway of the mitochondrial pyruvate dehydrogenase complex. Molecular Cell 82(5). Elsevier Inc.: 1066-1077.e7. DOI: 10.1016/j.molcel.2022.02.003.