Editing Mitochondrion (section)

===Replication and inheritance===
{{Main|Mitochondrial fission}}
Mitochondria divide by [[mitochondrial fission]], a form of [[binary fission]] that is also done by bacteria<ref>{{cite book| vauthors = Pfeiffer RF |title=Parkinson's Disease|year=2012|publisher=CRC Press|page=583|url=https://books.google.com/books?id=uWI0Ia3mkf8C&pg=PA583 |isbn=978-1439807149 }}</ref> although the process is tightly regulated by the host eukaryotic cell and involves communication between and contact with several other organelles. The regulation of this division differs between eukaryotes. In many single-celled eukaryotes, their growth and division are linked to the [[cell cycle]]. For example, a single mitochondrion may divide synchronously with the nucleus. This division and segregation process must be tightly controlled so that each daughter cell receives at least one mitochondrion. In other eukaryotes (in mammals for example), mitochondria may replicate their DNA and divide mainly in response to the energy needs of the cell, rather than in phase with the cell cycle. When the energy needs of a cell are high, mitochondria grow and divide. When energy use is low, mitochondria are destroyed or become inactive. In such examples mitochondria are apparently randomly distributed to the daughter cells during the division of the [[cytoplasm]]. Mitochondrial dynamics, the balance between [[mitochondrial fusion]] and [[mitochondrial fission|fission]], is an important factor in pathologies associated with several disease conditions.<ref>{{cite journal | vauthors = Seo AY, Joseph AM, Dutta D, Hwang JC, Aris JP, Leeuwenburgh C | title = New insights into the role of mitochondria in aging: mitochondrial dynamics and more | journal = Journal of Cell Science | volume = 123 | issue = Pt 15 | pages = 2533–2542 | date = August 2010 | pmid = 20940129 | pmc = 2912461 | doi = 10.1242/jcs.070490 }}</ref>

The hypothesis of mitochondrial binary fission has relied on the visualization by fluorescence microscopy and conventional [[transmission electron microscopy]] (TEM). The resolution of fluorescence microscopy (≈200&nbsp;nm) is insufficient to distinguish structural details, such as double mitochondrial membrane in mitochondrial division or even to distinguish individual mitochondria when several are close together. Conventional TEM has also some technical limitations{{which|date=January 2016}} in verifying mitochondrial division. [[Cryo-electron tomography]] was recently used to visualize mitochondrial division in frozen hydrated intact cells. It revealed that mitochondria divide by budding.<ref>{{cite journal | vauthors = Hu GB | title = Whole cell cryo-electron tomography suggests mitochondria divide by budding | journal = Microscopy and Microanalysis | volume = 20 | issue = 4 | pages = 1180–1187 | date = August 2014 | pmid = 24870811 | doi = 10.1017/S1431927614001317 | bibcode = 2014MiMic..20.1180H }}</ref>

An individual's mitochondrial genes are inherited only from the mother, with rare exceptions.<ref name="McWilliams-2019">{{cite journal | vauthors = McWilliams TG, Suomalainen A | title = Mitochondrial DNA can be inherited from fathers, not just mothers | journal = Nature | volume = 565 | issue = 7739 | pages = 296–297 | date = January 2019 | pmid = 30643304 | doi = 10.1038/d41586-019-00093-1 | doi-access = free | bibcode = 2019Natur.565..296M }}</ref> In humans, when an [[ovum|egg cell]] is fertilized by a sperm, the mitochondria, and therefore the mitochondrial DNA, usually come from the egg only. The sperm's mitochondria enter the egg, but do not contribute genetic information to the embryo.<ref>Kimball, J.W. (2006) [http://home.comcast.net/~john.kimball1/BiologyPages/S/Sexual_Reproduction.html#Copulation_and_Fertilization "Sexual Reproduction in Humans: Copulation and Fertilization"] {{Webarchive|url=https://web.archive.org/web/20151002175927/http://home.comcast.net/~john.kimball1/BiologyPages/S/Sexual_Reproduction.html#Copulation_and_Fertilization |date=October 2, 2015 }}, ''Kimball's Biology Pages'' (based on ''Biology'', 6th ed., 1996)</ref> Instead, paternal mitochondria are marked with [[ubiquitin]] to select them for later destruction inside the [[embryo]].<ref>{{cite journal | vauthors = Sutovsky P, Moreno RD, Ramalho-Santos J, Dominko T, Simerly C, Schatten G | title = Ubiquitin tag for sperm mitochondria | journal = Nature | volume = 402 | issue = 6760 | pages = 371–372 | date = November 1999 | pmid = 10586873 | doi = 10.1038/46466 | bibcode = 1999Natur.402..371S }} Discussed in [http://www.sciencenews.org/20000101/fob3.asp ''Science News''] {{Webarchive|url=https://web.archive.org/web/20071219174548/http://www.sciencenews.org/20000101/fob3.asp |date=December 19, 2007 }}.</ref> The egg cell contains relatively few mitochondria, but these mitochondria divide to populate the cells of the adult organism. This mode is seen in most organisms, including the majority of animals. However, mitochondria in some species can sometimes be inherited paternally. This is the norm among certain [[conifer]]ous plants, although not in [[pine tree]]s and [[taxus|yew]]s.<ref>{{cite journal |author=Mogensen HL|year=1996 |title=The Hows and Whys of Cytoplasmic Inheritance in Seed Plants |journal=American Journal of Botany |volume=83 |pages=383–404 |doi=10.2307/2446172 |issue=3 |jstor=2446172}}</ref> For [[Mytilidae|Mytilids]]<!--'Mytilidae mussels' just sounds wrong to me, unlike 'mussels of the family Mytilidae'. But, by analogy with members of canidae = canids etc., why not use 'Mytilids'?-->, paternal inheritance only occurs within males of the species.<ref>{{cite journal | vauthors = Zouros E | title = The exceptional mitochondrial DNA system of the mussel family Mytilidae | journal = Genes & Genetic Systems | volume = 75 | issue = 6 | pages = 313–318 | date = December 2000 | pmid = 11280005 | doi = 10.1266/ggs.75.313 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Sutherland B, Stewart D, Kenchington ER, Zouros E | title = The fate of paternal mitochondrial DNA in developing female mussels, Mytilus edulis: implications for the mechanism of doubly uniparental inheritance of mitochondrial DNA | journal = Genetics | volume = 148 | issue = 1 | pages = 341–347 | date = January 1998 | pmid = 9475744 | pmc = 1459795 | doi = 10.1093/genetics/148.1.341 }}</ref><ref>[http://mbe.library.arizona.edu/data/1995/1205/3stew.pdf Male and Female Mitochondrial DNA Lineages in the Blue Mussel ''(Mytilus edulis)'' Species Group] {{Webarchive|url=https://web.archive.org/web/20130518011756/http://mbe.library.arizona.edu/data/1995/1205/3stew.pdf |date=May 18, 2013 }} by Donald T. Stewart, Carlos Saavedra, Rebecca R. Stanwood, Amy 0. Ball, and Eleftherios Zouros</ref> It has been suggested that it occurs at a very low level in humans.<ref>{{cite journal | vauthors = Johns DR | title = Paternal transmission of mitochondrial DNA is (fortunately) rare | journal = Annals of Neurology | volume = 54 | issue = 4 | pages = 422–424 | date = October 2003 | pmid = 14520651 | doi = 10.1002/ana.10771 }}</ref>

[[Uniparental inheritance]] leads to little opportunity for [[genetic recombination]] between different lineages of mitochondria, although a single mitochondrion can contain 2–10 copies of its DNA.<ref name="Wiesner-1992"/> What recombination does take place maintains genetic integrity rather than maintaining diversity. However, there are studies showing evidence of recombination in mitochondrial DNA. It is clear that the enzymes necessary for recombination are present in mammalian cells.<ref>{{cite journal | vauthors = Thyagarajan B, Padua RA, Campbell C | title = Mammalian mitochondria possess homologous DNA recombination activity | journal = The Journal of Biological Chemistry | volume = 271 | issue = 44 | pages = 27536–27543 | date = November 1996 | pmid = 8910339 | doi = 10.1074/jbc.271.44.27536 | doi-access = free }}</ref> Further, evidence suggests that animal mitochondria can undergo recombination.<ref>{{cite journal | vauthors = Lunt DH, Hyman BC | title = Animal mitochondrial DNA recombination | journal = Nature | volume = 387 | issue = 6630 | pages = 247 | date = May 1997 | pmid = 9153388 | doi = 10.1038/387247a0 | doi-access = free | bibcode = 1997Natur.387..247L }}</ref> The data are more controversial in humans, although indirect evidence of recombination exists.<ref>{{cite journal | vauthors = Eyre-Walker A, Smith NH, Smith JM | title = How clonal are human mitochondria? | journal = Proceedings. Biological Sciences | volume = 266 | issue = 1418 | pages = 477–483 | date = March 1999 | pmid = 10189711 | pmc = 1689787 | doi = 10.1098/rspb.1999.0662 }}</ref><ref>{{cite journal | vauthors = Awadalla P, Eyre-Walker A, Smith JM | title = Linkage disequilibrium and recombination in hominid mitochondrial DNA | journal = Science | volume = 286 | issue = 5449 | pages = 2524–2525 | date = December 1999 | pmid = 10617471 | doi = 10.1126/science.286.5449.2524 }}</ref>

Entities undergoing uniparental inheritance and with little to no recombination may be expected to be subject to [[Muller's ratchet]], the accumulation of deleterious mutations until functionality is lost. Animal populations of mitochondria avoid this buildup through a developmental process known as the [[Heteroplasmy#Mitochondrial bottleneck|mtDNA bottleneck]]. The bottleneck exploits [[cellular noise|stochastic processes in the cell]] to increase the cell-to-cell variability in [[heteroplasmy|mutant load]] as an organism develops: a single egg cell with some proportion of mutant mtDNA thus produces an embryo where different cells have different mutant loads. Cell-level selection may then act to remove those cells with more mutant mtDNA, leading to a stabilization or reduction in mutant load between generations. The mechanism underlying the bottleneck is debated,<ref>{{cite journal | vauthors = Cree LM, Samuels DC, de Sousa Lopes SC, Rajasimha HK, Wonnapinij P, Mann JR, Dahl HH, Chinnery PF | title = A reduction of mitochondrial DNA molecules during embryogenesis explains the rapid segregation of genotypes | journal = Nature Genetics | volume = 40 | issue = 2 | pages = 249–254 | date = February 2008 | pmid = 18223651 | doi = 10.1038/ng.2007.63 }}</ref><ref>{{cite journal | vauthors = Cao L, Shitara H, Horii T, Nagao Y, Imai H, Abe K, Hara T, Hayashi J, Yonekawa H | title = The mitochondrial bottleneck occurs without reduction of mtDNA content in female mouse germ cells | journal = Nature Genetics | volume = 39 | issue = 3 | pages = 386–390 | date = March 2007 | pmid = 17293866 | doi = 10.1038/ng1970 }}</ref><ref>{{cite journal | vauthors = Wai T, Teoli D, Shoubridge EA | title = The mitochondrial DNA genetic bottleneck results from replication of a subpopulation of genomes | journal = Nature Genetics | volume = 40 | issue = 12 | pages = 1484–1488 | date = December 2008 | pmid = 19029901 | doi = 10.1038/ng.258 }}</ref> with a recent mathematical and experimental metastudy providing evidence for a combination of random partitioning of mtDNAs at cell divisions and random turnover of mtDNA molecules within the cell.<ref>{{cite journal | vauthors = Johnston IG, Burgstaller JP, Havlicek V, Kolbe T, Rülicke T, Brem G, Poulton J, Jones NS | title = Stochastic modelling, Bayesian inference, and new in vivo measurements elucidate the debated mtDNA bottleneck mechanism | journal = eLife | volume = 4 | pages = e07464 | date = June 2015 | pmid = 26035426 | pmc = 4486817 | doi = 10.7554/eLife.07464 | arxiv = 1512.02988 | doi-access = free }}</ref>