Mitochondrial dynamics and aging: Mitochondrial interaction preventing individuals form expression of respiratory deficiency caused by mutant mtDNA.

[timo...@my-deja.com]

Biochim Biophys Acta. 2006 Mar 24; [Epub ahead of print] Related
Articles, Links

Mitochondrial dynamics and aging: Mitochondrial interaction preventing
individuals form expression of respiratory deficiency caused by mutant
mtDNA.

Sato A, Nakada K, Hayashi JI.

Graduate School of Life and Environmental Sciences, University of
Tsukuba, Ibaraki 305-8572, Japan; Center for Tsukuba Advanced Research
Alliance (TARA), University of Tsukuba, Ibaraki 305-8572, Japan;
Department of Laboratory Animal Science, The Tokyo Metropolitan
Institute of Medical Science, Tokyo 113-8613, Japan.

In mammalian cells, there is an extensive and continuous exchange of
mitochondrial DNA (mtDNA) and its products between mitochondria. This
mitochondrial complementation prevents individuals from expression of
respiration deficiency caused by mutant mtDNAs. Thus, the presence of
mitochondrial complementation does not support the generally accepted
mitochondrial theory of aging, which proposes that accumulation of
somatic mutations in mtDNA is responsible for age-associated
mitochondrial dysfunction. Moreover, the presence of mitochondrial
complementation enables gene therapy for mitochondrial diseases using
nuclear transplantation of zygotes.

PMID: 16624428 [PubMed - as supplied by publisher]

[Hormesis]

What about the recent findings of widespread deletions on the order of
60% in mitochondria of the substantia nigra?

[Hormesis]

Excuse me. I should have said "approaching 50%."

rs10...@yahoo.com wrote:
> http://www.the-scientist.com/news/display/23324/

To evaluate the total load of mtDNA deletions in the substantia nigra,
Khrapko and his colleagues collected 80 pigmented cells from
individuals between 33 and 102 years old. They found significantly more

deletions in aged neurons than in young neurons. These aged cells often

possessed extremely high levels of deletions -- many showed more than
60% deleted mtDNA, which is considered the phenotypic threshold above
which respiratory function of the cell becomes impaired.

Working independently, researchers led by Douglass Turnbull of the
University of Newcastle upon Tyne, UK, also found very high levels of
deleted mtDNA in the substantia nigra of both aged people and people
with Parkinson disease. The substantia nigra pigmented cells show
"very, very high levels of deleted mtDNA," Turnbull said. "Previous
studies in other tissues had reported levels of 0.1-2%, whereas in the
substantia nigra neurons it is approaching 50%."

....
But "it's absolutely clear that the substantia nigra is the place where

the deletions accumulate to the highest level, not only in the brain,
but in the whole body," Cortopassi said. This brain region probably
accumulates such high levels of mtDNA deletions because dopamine
metabolism produces reactive oxygen species, which then create "a
massive amount of oxidative stress," Cortopassi said. "If we're looking

for a tissue and a disease in which mitochondrial mutations make a
really big difference in aging, this is the place to look."

[timo...@my-deja.com]

I don't agree with their proposition. However the mtFRA needs to
account for this. The results they are reporting obviously don't seem
to be happening in vivo. It does perhaps offer the hope that
mitochondria may be reparable.

Tim

[Hormesis]

You don't agree with their hypothesis of the cause of the deletion
levels or the actual deletion levels themselves?

What makes you say it's not happening in vivo in this particular region
of the brain?