Preliminary study of a new
deletion of mitochondria DNA fragment in human peripheral blood cells and its relation to the aging--《Chinese Journal of Geriatrics》2001年02期
Preliminary study of a new
deletion of mitochondria DNA fragment in human peripheral blood cells and its relation to the aging
?, WANG Xuemin, JIANG Lei,
?Department of Clinical Laboratory Diagnosis, Changhai Hospital of
Second Military Medical University, Shanghai 200433,China
To screen a new deletion in mitochondria(mtDNA) fragment in human peripheral blood cells, and study the relationship between the mtDNA deletion and the aging.
DNA extracted from human peripheral blood cells was used as PCR templates. The PCR products were cloned and sequenced. Semi
quantitative PCR was also used in detecting the ratio of deleted mtDNA to wild type mtDNA.
There was a 13
1 kb mtDNA deleted in human peripheral blood cells, and the deletion ratio between 60 age group and ≥60 age group was significantly different.
Conclusions
To our knowledge,this deletion has not been reported before and was the longest deleted fragment in human mitochondrial genome and it might be an aging
related deletion mutation.
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(C)2006 Tsinghua Tongfang Knowledge Network Technology Co., Ltd.(Beijing)(TTKN) All rights reservedMitochondria
Mitochondria
Mitochondria are the energy factories of the . The energy currency for the work that animals must do is the energy-rich molecule adenosine triphosphate (). The ATP is produced in the mitochondria using energy stored in food. Just as the
in plants act as sugar factories for the supply of ordered molecules to the plant, the mitochondria in animals and plants act to produce the ordered ATP molecules as the energy supply for the processes of life.
A typical animal cell will have on the order of 1000 to 2000 mitochondria. So the cell will have a lot of structures that are capable of producing a high amount of available energy. This ATP production by the mitochondria is done by the process of , which in essence is the use of oxygen in a process which generates energy. This is a very efficient process for using food energy to make ATP.
One of the benefits of "aerobic exercise" is that it improves your body's ability to make ATP rapidly using the respiration process.
All living cells have mitochondria. Hair cells and outer skin cells are dead cells and no longer actively producing ATP, but all cells have the same structure. Some cells have more mitochondria than others. Your fat cells have many mitochondria because they store a lot of energy. Muscle cells have many mitochondria, which allows them to respond quickly to the need for doing work. Mitochondria occupy 15 to 20 percent of mammalian liver cells according to Karp.
ReferenceCh 5
&*****R NaveHuman mitochondrial DNA replication.
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2012 Dec 1;4(12). pii: a012971. doi: 10.1101/cshperspect.a012971.Human mitochondrial DNA replication.1, .1MRC Mitochondrial Biology Unit, Cambridge, United Kingdom. ih@mrc-mbu.cam.ac.ukAbstractElucidation of the process of DNA replication in mitochondria is in its infancy. For many years, maintenance of the mitochondrial genome was regarded as greatly simplified compared to the nucleus. Mammalian mitochondria were reported to lack all DNA repair systems, to eschew DNA recombination, and to possess but a single DNA polymerase, polymerase γ. Polγ was said to replicate mitochondrial DNA exclusively via one mechanism, involving only two priming events and a handful of proteins. In this "strand-displacement model," leading strand DNA synthesis begins at a specific site and advances approximately two-thirds of the way around the molecule before DNA synthesis is initiated on the "lagging" strand. Although the displaced strand was long-held to be coated with protein, RNA has more recently been proposed in its place. Furthermore, mitochondrial DNA molecules with all the features of products of conventional bidirectional replication have been documented, suggesting that the process and regulation of replication in mitochondria is complex, as befits a genome that is a core factor in human health and longevity.PMID:
[PubMed - indexed for MEDLINE] Schematic diagram of the human mitochondrial genome. Human mtDNA encodes 13 proteins that are essential for oxidative phosphorylation, and the ribosomal and transfer RNAs necessary for their translation. RITOLS replication initiates in the major noncoding region, at OH and Ori-b, and OL is a major initiation site of lagging strand DNA synthesis in mammals. Conversely, conventional bidirectional replication of mtDNA can initiate almost anywhere in the mitochondrial genome, with most such events occurring in a region of several kilobases adjacent to the major noncoding region (NCR), Ori-z (see main text for details). LSP, l HSP, h CSBs, conserved sequence blocks.Cold Spring Harb Perspect Biol. ):a012971.Some mitochondrial replication intermediates form standard replication fork arcs and are resistant to single-strand nuclease. In the example shown mouse liver mtDNA was digested with DraI and half the digested was additionally treated with S1 nuclease prior to 2D-AGE. After blotting the DraI filter was hybridized with probe that detected a 4.5 kb fragment of mouse mtDNA, np 5 276–9 817. ssDNA, single-stranded DNA; ds mtRIs, double-stranded mitochondrial replication intermediates.Cold Spring Harb Perspect Biol. ):a012971.Replicating molecules of mtDNA produce duplex slow-moving arcs, which are sensitive to RNase H. (A) 2D-AGE of BclI digested mouse liver mtDNA reveals a pair of slow-moving replication fork (SMY) arcs, after hybridization to a probe detecting the 4 kb fragment nucleotides 12,027–16,174. SMY arcs result from blocked restriction sites and are essentially duplex, based on their mass, arc i has a theoretical mass of 13,096 bp initially, increasing to 17,341 bp if fully duplex, whereas it would begin at 10,744 and end at 12,866 bp if it contained a single-stranded DNA branch. Arc ii spans 17,078–21,060 12,603–14,594 if it follows SDM. The spans of the arcs predicted by SDM are indicated in gray font, as no such arcs were detected when gradient-purified mtDNA was analyzed. (B) 2D-AGE of AccI digested mouse liver mtDNA reveals a slow-moving replication fork (SMY) arc, after hybridization to a probe detecting the 5-kb fragment, nucleotides . N.B., AccI cleaves both single-stranded and double-stranded DNA. Dashed line corresponds to the expected arc in the case of SDM replication. (C) The same digest of purified mouse liver mtDNA as shown in panel A was incubated with and without RNase H and single-stranded (S1) nuclease, and analyzed by 2D-AGE. SMY arcs are inferred to have ribonucleotides at one or more restriction sites, in part because the SMY arcs are grossly modified by RNase H. Similarly, bubble arc b2 is also sensitive to RNase H and therefore contains significant amounts of RNA, as opposed to bubble arc b1; see also main text and
for details.Cold Spring Harb Perspect Biol. ):a012971.The RITOLS model of mitochondrial DNA replication. Replication initiates at one of two sites (OH or Ori-b), here conflated to OR, for origin of replication. Leading strand DNA synthesis progresses with concurrent incorporation of RNA on the lagging strand. At some point (frequently OL), lagging strand DNA synthesis initiates and the lagging strand RNA is replaced by, or converted to, DNA.Cold Spring Harb Perspect Biol. ):a012971.Maturation of RITOLS RNA, and the formation of free 5′ ends of DNA during DNA replication. Replication stalling is associated with an increase in fully duplex DNA intermediates, which could be the result of RNA replacement with DNA (A). This could be the result of strand-switching by the replicative DNA polymerase. (B) One of a pair of replication forks derived from a bidirectional origin of replication has just reached the terminus (Ter) causing arrest of leading strand DNA the Okazaki fragments are joined to make the lagging strand continuous, leaving a single free 5′ end remaining at the terminus, whereas the origin is no longer detectable.Cold Spring Harb Perspect Biol. ):a012971.Publication TypesMeSH TermsSubstancesGrant SupportFull Text Sources
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