Amitosis

Amitosis, also known as karyostenosis, direct cell division, or binary fission, represents a mode of asexual cell division predominantly observed in prokaryotes. This process is distinct from other cell division mechanisms such as mitosis and meiosis, primarily 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 division of the cell occurs, simplifying the process of cellular replication.

Several instances of cell division formerly thought to be "non-mitotic", such as the division of some unicellular eukaryotes, may actually occur by the process of "closed mitosis", which is different from open or semi-closed mitotic processes, all of which involve mitotic chromosomes and are classified by nuclear envelope. Amitosis can also affect the distribution of human lactic acid dehydrogenase isoenzyme, which is present in almost all body tissue. An example of amitosis is spermatogenesis. When in the process of amitosis, the cell membrane will not divide.

Cells containing two or more nuclei are called binucleated and multinucleated cells, respectively. Sometimes this is also caused by the fusion of cells. Amitosis differs fundamentally from mitosis without cytokinesis, yet some similarities are shared between amitosis and cell fusion. Amitosis can result in near haploid nuclei, which is not possible through mitosis or cell fusion.

The mitotic index declines from 2.2% at day ten to 0.3% at day thirty during postnatal life. Delayed fixation yields degenerated prophase and telophase nuclei only.

Processes
Amitosis is the division of cells in the interphase state, usually accomplished by a simple constriction into two sometimes unequal halves without any regular segregation of genetic material. As a result, this process leads to the random distribution of parental chromosomes in the subsequent daughter cells, in contrast to mitosis, which involves the precise distribution of chromosomes in the resulting daughter cells. This phenomenon does not involve the maximal condensation of chromatin into chromosomes, a molecular event that is observable by light microscopy when sister chromatids line up in pairs along the metaphase plate. While amitosis has been reported in ciliates, its role in mammalian cell proliferation is still unconfirmed. The discovery of copy number variations (CNVs) in mammalian cells within an organ 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. Furthermore, ciliates possess a mechanism for adjusting copy numbers of individual genes during amitosis of the macronucleus.

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

Functional role
Additional reports of non-mitotic proliferation as well as insights into its underlying mechanisms have emerged from extensive work with polyploid cells. Multiple copies of the genome in a cell population may be involved in the cell's adaptation to the environment.

Polyploid cells are frequently "reduced" to diploid cells by amitosis. Naturally occurring polyploid placental cells have been observed to produce nuclei with diploid or near-diploid complements of DNA. Such nuclei, derived from polyploid placental cells, receive one or more copies of a microscopically identifiable region of the chromatin. This particular 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. Polyploid cells may also be key to the survival processes underlying chemotherapy resistance in certain cells.

It has been reported that following the treatment of cultured cells with mitosis-inhibiting chemicals (similar to those used in certain chemotherapeutic protocols), a small population of induced polyploid cells survive. Eventually, this population gives rise to "normal" diploid cells by the formation of polyploid chromatin bouquets that return to an interphase state, before separating into several secondary nuclei. The controlled autophagic degradation of DNA as well as the production of nuclear envelope-limited sheets accompany the process. Since this process of depolyploidization involves mitotic chromosomes, it conforms to the broad definition of amitosis.

Current literature
There are multiple reports of amitosis occurring when nuclei bud out through the plasma membrane of a polyploid cell. Such a process has been shown to occur in amniotic cells transformed by a virus and in mouse embryo fibroblast lines exposed to carcinogens. A similar process called extrusion has been described for mink trophoblasts, a tissue in which fissioning is also observed. 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. Similarly, two different kinds of amitosis have been described in monolayers of Ishikawa endometrial cells.

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. 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. Over the next 4 to 5 hours, chromatin from these aggregated nuclei becomes increasingly pycnotic, eventually undergoing karyolysis and karyorrhexis in the now-elevated predome structures. In other systems, such changes accompany apoptosis but not in the 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.

The scientific literature not only affirms the involvement of amitosis in cell proliferation, but also explores the existence of more than one amitotic mechanism capable of producing "progeny nuclei" without the involvement of "mitotic chromosomes." A form of amitosis involves fissioning, a nucleus splitting in two without the involvement of chromosomes, which has been reported to occur in placental tissues and in cells grown from such tissues in rats, as well as in human and mouse trophoblasts. Amitosis by fissioning has also been reported in mammalian liver cells and human adrenal cells. Chen and Wan 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 Mac amitosis of Tetrahymena, γ-tubulin-mediated MT assembly was required.

In other studies, 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.

The current body of literature suggests that amitosis may be involved in cellular development in humans, 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.