PMID- 9742236
OWN - NLM
STAT- MEDLINE
DCOM- 19981117
LR  - 20190501
IS  - 0305-1048 (Print)
IS  - 1362-4962 (Electronic)
IS  - 0305-1048 (Linking)
VI  - 26
IP  - 19
DP  - 1998 Oct 1
TI  - mtDNA replicative potential remains constant during ageing: polymerase gamma 
      activity does not correlate with age related cytochrome oxidase activity decline 
      in platelets.
PG  - 4365-73
AB  - Progressive age-related oxidative phosphorylation (OxPhos) decline is well known 
      in human tissues. Depletion of mitochondrial DNA (mtDNA) causes OxPhos defects in 
      patients with myopathic syndromes and deficient mtDNA replication has been 
      observed in cells cultured from patients with mitochondrial disease. Patients 
      undergoing treatment for AIDS develop OxPhos defects via mtDNA depletion 
      resulting from inhibition of mtDNA polymerase gamma (Polgamma) by 2'-deoxy 
      3'-azido thymidine. These findings by others give rise to a possible link between 
      mtDNA replication and bioenergetic decline in disease and during ageing. We have 
      designed an in vitro assay for Polgamma function in small tissue samples to 
      explore this possible link. Platelet homogenate Polgamma showed an activity with 
      a K m of 150 microM (dTTP), a V max of 11.8 pmol/min/mg, inhibited (41% 
      inhibition; 50 microM) by ethidium bromide. Determination of several storage 
      characteristics showed that platelets were a convenient source of Polgamma for 
      assay. Polgamma activity in 45 subjects did not coincide with significant 
      age-related decline (P<0.002; P) observed in cytochrome oxidase (CytOx) activity 
      or with citrate synthase activity. Of the activities studied, the only 
      significant age-wise variation was a 24% CytOx deficiency in elderly (>50; n = 
      19) compared to young (<51; n = 24) individuals (P<0.01; t). These results 
      suggest a maintenance of total cellular mtDNA Polgamma processive levels during 
      ageing, largely independent of total cellular bioenergetic status or 
      mitochondrial number/density. The processive component of Polgamma is therefore 
      unlikely to make a major contribution to age-related bioenergetic activity 
      decline. This does not, however, preclude the possibility that transient periods 
      of inhibition at crucial points of the cell cycle or development may augment 
      existing intracellular deficiencies. The assay described here greatly facilitates 
      study of Polgamma activity in patients with conditions involving mtDNA depletion 
      or rearrangement.
FAU - Kapsa, R M
AU  - Kapsa RM
AD  - Melbourne Neuromuscular Research Centre and Department of Clinical CSIRO Division 
      of Molecular Science, Parkville Laboratory, Parkville, Victoria 3052, Australia. 
      rkapsa@ariel.unimelb.edu.au
FAU - Quigley, A F
AU  - Quigley AF
FAU - Han, T F
AU  - Han TF
FAU - Jean-Francois, M J
AU  - Jean-Francois MJ
FAU - Vaughan, P
AU  - Vaughan P
FAU - Byrne, E
AU  - Byrne E
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Nucleic Acids Res
JT  - Nucleic acids research
JID - 0411011
RN  - 0 (DNA, Mitochondrial)
RN  - EC 1.9.3.1 (Electron Transport Complex IV)
RN  - EC 2.7.7.7 (DNA Polymerase gamma)
RN  - EC 2.7.7.7 (DNA-Directed DNA Polymerase)
SB  - IM
MH  - Adult
MH  - Aging/*genetics
MH  - DNA Polymerase gamma
MH  - *DNA Replication
MH  - DNA, Mitochondrial/*genetics/metabolism
MH  - DNA-Directed DNA Polymerase/genetics/*metabolism
MH  - Electron Transport Complex IV/genetics/*metabolism
MH  - Enzyme Activation
MH  - Humans
MH  - Middle Aged
PMC - PMC147866
EDAT- 1998/09/22 00:00
MHDA- 1998/09/22 00:01
PMCR- 1998/10/01
CRDT- 1998/09/22 00:00
PHST- 1998/09/22 00:00 [pubmed]
PHST- 1998/09/22 00:01 [medline]
PHST- 1998/09/22 00:00 [entrez]
PHST- 1998/10/01 00:00 [pmc-release]
AID - gkb713 [pii]
AID - 10.1093/nar/26.19.4365 [doi]
PST - ppublish
SO  - Nucleic Acids Res. 1998 Oct 1;26(19):4365-73. doi: 10.1093/nar/26.19.4365.