Amitosis

Amitosis, also known as karyostenosis, direct cell division, or binary fission, is a mode of asexual cell division primarily observed in prokaryotes. This process is distinct from other cell division mechanisms such as mitosis and meiosis, mainly because it bypasses the complexities associated with the mitotic apparatus, such as spindle formation. Additionally, amitosis does not involve the condensation of chromatin into distinct chromosomes before the cell divides, thereby simplifying the process of cellular replication.

Several instances of cell division previously thought to be "non-mitotic", such as the division of some unicellular eukaryotes, may actually occur by "closed mitosis",^[1] which differs from open or semi-closed mitotic processes. These processes involve mitotic chromosomes and are classified based on the condition of the nuclear envelope. Amitosis can also affect the distribution of human lactic acid dehydrogenase isoenzymes, which are present in almost all body tissues. An example of amitosis is spermatogenesis. During amitosis, the cell membrane does not divide.

Cells containing two or more nuclei are called binucleated and multinucleated cells, respectively, which can also result from the fusion of cells. Although amitosis differs fundamentally from mitosis without cytokinesis, some similarities exist between amitosis and cell fusion. Amitosis can result in nearly haploid nuclei, which is not possible through mitosis or cell fusion.^[2]

Discovery

Amitosis was first described in 1880 by Walther Flemming, who also described mitosis and other forms of cell division.^[3] Initially it was common for biologists to think of cells having the ability to divide both mitotically and amitotically.^[4]

Process

Amitosis is the division of cells in the interphase state, typically achieved by a simple constriction into two sometimes unequal halves without any regular segregation of genetic material.^[5] This process results in the random distribution of parental chromosomes in the daughter cells, in contrast to mitosis, which involves the precise distribution of chromosomes. Amitosis does not involve the maximal condensation of chromatin into chromosomes, a molecular event observable by light microscopy when sister chromatids align along the metaphase plate.

While amitosis has been reported in ciliates, its role in mammalian cell proliferation remains unconfirmed. The discovery of copy number variations (CNVs) in mammalian cells within an organ^[6] has challenged the assumption that every cell in an organism must inherit an exact copy of the parental genome to be functional. Instead of CNVs stemming from errors in mitosis, such variations could have arisen from amitosis and may even be beneficial to the cells. Additionally, ciliates possess a mechanism for adjusting the copy numbers of individual genes during amitosis of the macronucleus.^[7]

Mechanism

Additional reports of non-mitotic proliferation and insights into its underlying mechanisms have emerged from extensive work with polyploid cells. Multiple copies of the genome in a cell population may play a role in the cell's adaptation to the environment.^[8]

Polyploid cells are frequently "reduced" to diploid cells by amitosis.^[9] Naturally occurring polyploid placental cells have been observed to produce nuclei with diploid or near-diploid complements of DNA. These nuclei, derived from polyploid placental cells, receive one or more copies of a microscopically identifiable region of chromatin. This amitotic process can result in representative transmission of chromatin. In rat polyploid trophoblasts, the nuclear envelope of the giant nucleus is involved in this subdivision.^[10] Polyploid cells may also be key to the survival processes underlying chemotherapy resistance in certain cells.

Following the treatment of cultured cells with mitosis-inhibiting chemicals, similar to those used in some chemotherapeutic protocols, a small population of induced polyploid cells survives. Eventually, this population gives rise to "normal" diploid cells by forming polyploid chromatin bouquets that return to an interphase state before separating into several secondary nuclei.^[11] The controlled autophagic degradation of DNA and the production of nuclear envelope-limited sheets^[12] accompany the process.^[13] Since this process of depolyploidization involves mitotic chromosomes, it conforms to the broad definition of amitosis.

The scientific literature affirms the involvement of amitosis in cell proliferation and explores multiple amitotic mechanisms capable of producing "progeny nuclei" without "mitotic chromosomes." One form of amitosis involves fissioning, where a nucleus splits in two without involving chromosomes. This has been reported in placental tissues and cells grown from such tissues in rats,^[14] as well as in human and mouse trophoblasts.^[15]^[2] Amitosis by fissioning has also been reported in mammalian liver cells^[16] and human adrenal cells.^[17] Chen and Wan^[18] reported amitosis in rat liver and presented a mechanism for a four-stage amitotic process whereby chromatin threads are reproduced and equally distributed to daughter cells as the nucleus splits in two. In macronuclear amitosis of Tetrahymena, γ-tubulin-mediated MT assembly was required.^[19]

There are multiple reports of amitosis occurring when nuclei bud out through the plasma membrane of a polyploid cell. This process has been observed in amniotic cells transformed by a virus^[20] and in mouse embryo fibroblast lines exposed to carcinogens.^[21] A similar process called extrusion has been described for mink trophoblasts, a tissue in which fissioning is also observed.^[22] Asymmetric cell division has also been described in polyploid giant cancer cells and low eukaryotic cells and is reported to occur by the amitotic processes of splitting, budding, or burst-like mechanisms.^[23]

Examples

An example of amitosis particularly suited to the formation of multiple differentiated nuclei in a reasonably short period of time has been shown to occur during the differentiation of fluid-enclosing hemispheres called domes from adherent Ishikawa endometrial monolayer cells during an approximately 20-hour period.^[24]^[25] During the initial stages of differentiation, particularly within the first 6 hours, aggregates of nuclei from monolayer syncytia undergo a unique process where they become enveloped in mitochondrial membranes. These resulting structures, known as mitonucleons, experience an elevation due to the formation of vacuoles around them. This phenomenon indicates a distinct cellular organization and differentiation process, highlighting the complex interactions between cellular structures during development.^[26] In other systems, such changes accompany apoptosis, but not in differentiating Ishikawa cells, where the processes appear to accompany changes in DNA essential for the newly created, differentiated dome cells. Finally, the chromatin filaments emerging from these processes form a mass from which dozens of dome nuclei are amitotically generated over approximately 3 hours with the apparent involvement of nuclear envelope-limited sheets.^[12]

In development

Examination of fetal guts during development (5 to 7 weeks), colonic adenomas, and adenocarcinomas has revealed nuclei that appear as hollow bells encased in tubular syncytia. These structures can either divide symmetrically by an amitotic nuclear fission process, forming new "bells", or undergo fission asymmetrically, resulting in one of seven other nuclear morphotypes, five of which appear to be specific to development since they are rarely observed in adult organisms.^[27]

The current body of literature suggests that amitosis may be involved in cellular development in humans,^[8] likely during the fetal and embryonic phases of development when the majority of these cells are produced.

When the intestinal stem cells (ISCs) in fruit flies' guts are seriously reduced, they use amitosis to repair the damage. Cells in another part of the gut, called enterocytes, reduce the number of chromosomes without going through the normal division process. This helps replace the lost ISCs, keeping the gut functioning properly.^[28]

References

^ Güttinger S, Laurell E, Kutay U (March 2009). "Orchestrating nuclear envelope disassembly and reassembly during mitosis". Nature Reviews. Molecular Cell Biology. 10 (3): 178–191. doi:10.1038/nrm2641. PMID 19234477.
^ ^a ^b Kuhn EM, Therman E, Susman B (1991). "Amitosis and endocycles in early cultured mouse trophoblast". Placenta. 12 (3): 251–261. doi:10.1016/0143-4004(91)90006-2. PMID 1754574.
^ Macklin CC (June 1916). "Amitosis in Cells Growing in Vitro". The Biological Bulletin. 30 (6): 445–[466]–1. doi:10.2307/1536358. ISSN 0006-3185. JSTOR 1536358.
^ Holland N (2021). "Vicenzo Colucci's 1886 memoir, Intorno alla rigenerazione degli arti e della coda nei tritoni, annotated and translated into English as: Concerning regeneration of the limbs and tail in salamanders". The European Zoological Journal. 88: 837–890. doi:10.1080/24750263.2021.1943549. S2CID 238904520.
^ Tippit DH, Pickett-Heaps JD (July 1976). "Apparent amitosis in the binucleate dinoflagellate Peridinium balticum". Journal of Cell Science. 21 (2): 273–289. doi:10.1242/jcs.21.2.273. PMID 987046.
^ O'Huallachain M, Karczewski KJ, Weissman SM, Urban AE, Snyder MP (October 2012). "Extensive genetic variation in somatic human tissues". Proceedings of the National Academy of Sciences of the United States of America. 109 (44): 18018–18023. Bibcode:2012PNAS..10918018O. doi:10.1073/pnas.1213736109. PMC 3497787. PMID 23043118.
^ Prescott DM (June 1994). "The DNA of ciliated protozoa". Microbiological Reviews. 58 (2): 233–267. doi:10.1128/MMBR.58.2.233-267.1994. PMC 372963. PMID 8078435.
^ ^a ^b Duncan AW, Taylor MH, Hickey RD, Hanlon Newell AE, Lenzi ML, Olson SB, et al. (October 2010). "The ploidy conveyor of mature hepatocytes as a source of genetic variation". Nature. 467 (7316): 707–710. Bibcode:2010Natur.467..707D. doi:10.1038/nature09414. PMC 2967727. PMID 20861837.
^ Zybina TG, Zybina EV, Kiknadze II, Zhelezova AI (May 2001). "Polyploidization in the trophoblast and uterine glandular epithelium of the endotheliochorial placenta of silver fox (Vulpes fulvus Desm.), as revealed by the DNA content". Placenta. 22 (5): 490–498. doi:10.1053/plac.2001.0675. PMID 11373160.
^ Zybina EV, Zybina TG (July 2008). "Modifications of nuclear envelope during differentiation and depolyploidization of rat trophoblast cells". Micron. 39 (5): 593–606. doi:10.1016/j.micron.2007.05.006. PMID 17627829.
^ Erenpreisa J, Salmina K, Huna A, Kosmacek EA, Cragg MS, Ianzini F, et al. (July 2011). "Polyploid tumour cells elicit paradiploid progeny through depolyploidizing divisions and regulated autophagic degradation". Cell Biology International. 35 (7): 687–695. doi:10.1042/CBI20100762. PMID 21250945. S2CID 130498.
^ ^a ^b Olins AL, Buendia B, Herrmann H, Lichter P, Olins DE (November 1998). "Retinoic acid induction of nuclear envelope-limited chromatin sheets in HL-60". Experimental Cell Research. 245 (1): 91–104. doi:10.1006/excr.1998.4210. PMID 9828104.
^ Erenpreisa J, Ivanov A, Cragg M, Selivanova G, Illidge T (March 2002). "Nuclear envelope-limited chromatin sheets are part of mitotic death". Histochemistry and Cell Biology. 117 (3): 243–255. doi:10.1007/s00418-002-0382-6. PMID 11914922. S2CID 7261907.
^ Ferguson FG, Palm J (February 1976). "Histologic characteristics of cells cultured from rat placental tissue". American Journal of Obstetrics and Gynecology. 124 (4): 415–420. doi:10.1016/0002-9378(76)90103-4. PMID 1251862.
^ Cotte C, Easty GC, Neville AM, Monaghan P (August 1980). "Preparation of highly purified cytotrophoblast from human placenta with subsequent modulation to form syncytiotrophoblast in monolayer cultures". In Vitro. 16 (8): 639–646. doi:10.1007/bf02619191. PMID 7419234. S2CID 20834295.
^ David H, Uerlings I (September 1992). "[Ultrastructure of amitosis and mitosis of the liver]". Zentralblatt Fur Pathologie. 138 (4): 278–283. PMID 1420108.
^ Magalhães MC, Pignatelli D, Magalhães MM (April 1991). "Amitosis in human adrenal cells". Histology and Histopathology. 6 (2): 251–256. PMID 1802124.
^ Chen YQ, Wan BK (1986). "A study on amitosis of the nucleus of the mammalian cell. I. A study under the light and transmission electron microscope". Acta Anatomica. 127 (1): 69–76. doi:10.1159/000146240. PMID 3788448.
^ Kushida Y, Nakano K, Numata O (February 2011). "Amitosis requires γ-tubulin-mediated microtubule assembly in Tetrahymena thermophila". Cytoskeleton. 68 (2): 89–96. doi:10.1002/cm.20496. PMID 21246753.
^ Walen KH (February 2002). "The origin of transformed cells. studies of spontaneous and induced cell transformation in cell cultures from marsupials, a snail, and human amniocytes". Cancer Genetics and Cytogenetics. 133 (1): 45–54. doi:10.1016/s0165-4608(01)00572-6. PMID 11890989.
^ Sundaram M, Guernsey DL, Rajaraman MM, Rajaraman R (February 2004). "Neosis: a novel type of cell division in cancer". Cancer Biology & Therapy. 3 (2): 207–218. doi:10.4161/cbt.3.2.663. PMID 14726689.
^ Isakova GK, Shilova IE (July 2003). "[Frequency ratio of two forms of amitotic division of trophoblast cell nuclei in the mink blastocysts during the period of delayed implantation]". Izvestiia Akademii Nauk. Seriia Biologicheskaia (4): 395–398. PMID 12942744.
^ Zhang D, Wang Y, Zhang S (2014). "Asymmetric cell division in polyploid giant cancer cells and low eukaryotic cells". BioMed Research International. 2014: 432652. doi:10.1155/2014/432652. PMC 4089188. PMID 25045675.
^ Fleming H (February 1995). "Differentiation in human endometrial cells in monolayer culture: dependence on a factor in fetal bovine serum". Journal of Cellular Biochemistry. 57 (2): 262–270. doi:10.1002/jcb.240570210. PMID 7759563. S2CID 40483780.
^ Fleming H (1999). "Structure and function of cultured endometrial epithelial cells". Seminars in Reproductive Endocrinology. 17 (1): 93–106. doi:10.1055/s-2007-1016215. PMID 10406079. S2CID 9681391.
^ Fleming H, Condon R, Peterson G, Guck I, Prescott E, Chatfield K, et al. (December 1998). "Role of biotin-containing membranes and nuclear distribution in differentiating human endometrial cells". Journal of Cellular Biochemistry. 71 (3): 400–415. doi:10.1002/(SICI)1097-4644(19981201)71:3<400::AID-JCB9>3.0.CO;2-W. PMID 9831077. S2CID 19080155.
^ Gostjeva EV, Zukerberg L, Chung D, Thilly WG (January 2006). "Bell-shaped nuclei dividing by symmetrical and asymmetrical nuclear fission have qualities of stem cells in human colonic embryogenesis and carcinogenesis". Cancer Genetics and Cytogenetics. 164 (1): 16–24. doi:10.1016/j.cancergencyto.2005.05.005. PMID 16364758.
^ Lucchetta EM, Ohlstein B (May 2017). "Amitosis of Polyploid Cells Regenerates Functional Stem Cells in the Drosophila Intestine". Cell Stem Cell. 20 (5): 609–620.e6. doi:10.1016/j.stem.2017.02.012. PMC 5419863. PMID 28343984.