How do mitochondria replicate and segregate?
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mtDNA replication and segregation to daughter mitochondria is stochastic.
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Mitochondrial segregation to daughter cells is also stochastic.
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Mitochondria must be duplicated during
the cell cycle and segregated to the daughter cells. We understand some
of the mechanics of this process, but not its regulation.
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At each stage in the duplication of mitochondria — DNA replication, DNA segregation to duplicate mitochondria,
organelle segregation to daughter cells — the process appears to be stochastic, governed by a random
distribution of each copy (for review see 2288).
The theory of distribution in this case is analogous that of multicopy
bacterial plasmids, with the same conclusion that >10 copies are
required to ensure that each daughter gains at least one copy
(see Single-copy plasmids have a partitioning system).
When there are mtDNAs with allelic variations (either because of
inheritance from different parents or because of mutation), the
stochastic distribution may generate cells that have only one of the
alleles.
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Replication of mtDNA may be stochastic
because there is no control over which particular copies are
replicated, so that in any cycle some mtDNA molecules may replicate
more times than others. The total number of copies of the genome may be
controlled by titrating mass in a way similar to bacteria
(see Replication is connected to the cell cycle ).
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A mitochondrion divides by developing a
ring around the organelle that constricts to pinch it into two halves.
The mechanism is similar in principle to that involved in bacterial
division. The apparatus that is used in plant cell mitochondria is
similar to bacteria and uses a homologue of the bacterial protein FtsZ
(see FtsZ is necessary for septum formation). The molecular
apparatus is different in animal cell mitochondria, and uses the
protein dynamin that is involved in formation of membranous vesicles
(see Different types of coated vesicles exist in each pathway).
An individual organelle may have more than one copy of its genome.
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Figure 13.44
Mitochondrial DNA replicates by increasing the number
of genomes in proportion to mitochondrial mass, but without ensuring
that each genome replicates the same number of times. This can lead to
changes in the representation of alleles in the daughter mitochondria.
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We do not know whether there is a partitioning mechanism for segregating mtDNA molecules within the
mitochondrion, or whether they are simply inherited by daughter
mitochondria according to which half of the mitochondrion they happen
to lie in. Figure 13.44 shows that the combination of replication and segregation mechanisms
can result in a stochastic assignment of DNA to each of the copies,
that is, so that the distribution of mitochondrial genomes to daughter
mitochondria does not depend on their parental origins.
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The assignment of mitochondria to daughter cells at mitosis also appears to be random. Indeed, it was the
observation of somatic variation in plants that first suggested the
existence of genes that could be lost from one of the daughter cells
because they were not inherited according to Mendel's laws (see Figure 3.37)
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In some situations a mitochondrion has
both paternal and maternal alleles. This has two requirements: that
both parents provide alleles to the zygote (which of course is not the
case when there is maternal inheritance; see Organelles have DNA);
and that the parental alleles are found in the same mitochondrion.
For this to happen, parental mitochondria must have fused.
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The size of the individual mitochondrion
may not be precisely defined. Indeed, there is a continuing question as
to whether an individual mitochondrion represents a unique and discrete
copy of the organelle or whether it is in a dynamic flux in which it
can fuse with other mitochondria. We know that mitochondria can fuse in
yeast, because recombination between mtDNAs can occur after two haploid
yeast strains have mated to produce a diploid strain. This implies that
the two mtDNAs must have been exposed to one another in the same
mitochondrial compartment. Attempts have been made to test for the
occurrence of similar events in animal cells by looking for
complementation between alleles after two cells have been fused, but
the results are not clear.
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Last Revised on 2-8-2002
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2288 Birky, C. W.
(2001).
The inheritance of genes in mitochondria and chloroplasts: laws, mechanisms, and models.
Annu. Rev. Genet. 35, 125-148.
PubMed Journal
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© Jones and Bartlett Publishers (2007)
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