Bad Mitochondria May Actually Be Good For You
Parijata Mackey
Bad mitochondria may actually be good for you
Posted by: Snowcrash on: July 22, 2009/
Mice with a defective mitochondrial protein called MCLK1 produce elevated amounts of reactive oxygen when young; that should spell disaster, yet according to a study in this week’s JBC these mice actually age at a slower rate and live longer than normal mice.
Mitochondrial oxidative stress is a popular theory explaining the aging process; over time, reactive oxygen species produced by mitochondria while they make energy slowly accumulate and begin damaging cells, including the mitochondria. Several recent studies have begun to question this theory, though, and to get some more direct answers, Siegfried Hekimi and colleagues at McGill University examined the mitochondria of MCLK1-defective mice, a strain known for its longevity, at various ages.
What they found was that in young (3 month old) MCLK1-defective mice, mitochondria were quite energy inefficient and produced a lot of harmful oxygen radicals; yet surprisingly, when these mice were 23 months old, their mitochondria were working better than normal mice. So, despite the oxidative stress, these mice experienced less deterioration than normal.
To confirm whether MCLK1-defiency could be somehow protective, the researchers crossed MCLK1-defective mice with those lacking SOD2, a major protein antioxidant. Normally, SOD2-defective mice accumulate cellular damage quickly, yet when combined with MCLK1-defiency, they exhibited less damage and oxidative stress.
In explaining this seeming paradox, Hekimi and colleagues suggest that while MCLK1-defective mice produce more oxygen radicals from their mitochondria, their overall inefficiency results in less energy and fewer oxygen radicals being produced in other parts of a cell. Thus while these mice may have some higher risks of damage while young, they accumulate less damage as they age –a finding that seems to indicate the mitochondrial stress theory may not be correct.
Source: American Society for Biochemistry and Molecular Biology
--Parijata Mackey
University of Chicago
pari...@gmail.com
www.parijata.com
--
"Have patience with all yet unsolved in your heart. Try to love the questions themselves, like locked rooms and foreign scripts. Do not now seek the answers. They cannot yet be given because you could not yet live them -- and the point is to live everything. At the present, you need to live the question. Perhaps you will gradually, without even noticing it, find yourself experiencing the answer, some distant day."
- Rainer Maria Rilke
caston
On Jul 23, 7:25 am, Parijata Mackey <parij...@gmail.com> wrote:
> Bad mitochondria may actually be good for you
> MCLK1-defective mice produce more oxygen radicals from their mitochondria,
> their overall inefficiency results in less energy and fewer oxygen radicals
> being produced in other parts of a cell. Thus while these mice may have some
> higher risks of damage while young, they accumulate less damage as they age
> –a finding that seems to indicate the mitochondrial stress theory may not be
> correct.
>
> Source: American Society for Biochemistry and Molecular
> Parijata Mackey
> University of Chicago
Increased oxygen radical production may yet prove not a bug but a
feature. I'd want to compare the intracellular microbiomes and
cellular organelles of the MCLK1-deficient mice compared to the
controls.
My theory is that these leaky free radicals is actually another weapon
of the intracellular immune system. Mitochondria get attacked by
pathogens in the cytoplasm and the only defense weapon they have are
free radicals.
The increasing levels of free radicals are not due to an error
catastrophe of increasing mutant mitochondria but rather a MAD arms
race in an increasingly hostile cytoplasm.
When the cell is free of pathogenic bacteria the mitochondria will
have sex and fuse together repairing damage and then making new
mitochondria through fission.
best regards,
Chris
Jim Lai
increased lifespan, which I'll quote in part:
http://www.eurekalert.org/pub_releases/2007-12/cp-fdo112707.php
By making the skeletal muscles of mice use energy less efficiently,
researchers report in the December issue of Cell Metabolism, a
publication of Cell Press, that they have delayed the animals’ deaths
and their development of age-related diseases, including vascular
disease, obesity, and one form of cancer. Those health benefits,
driven by an increased metabolic rate, appear to come without any
direct influence on the aging process itself, according to the
researchers.
The mitochondria powering the mouse muscles were made inefficient by
increasing the activity of so-called uncoupling protein 1 (UCP1). UCP1
disrupts the transfer of electrons from food to oxygen, a process
known as mitochondrial respiration, which normally yields the energy
transport molecule ATP. Instead, the energy is lost as heat.
“When you make the mitochondria inefficient, the muscles burn more
calories,” a metabolic increase that could be at least a partial
substitute for exercise, said Clay Semenkovich of Washington
University School of Medicine in St. Louis. “There are a couple of
ways to treat obesity and related diseases,” he continued. “You can
eat less, but that’s unpopular, or you could eat what you want as
these animals did and introduce an altered physiology. It’s a
fundamentally different way of addressing the problem.”
...
The researchers include Allison C. Gates, Carlos Bernal-Mizrachi,
Sharon L. Chinault, Chu Feng, Jochen G. Schneider, Trey Coleman, James
P. Malone, R. Reid Townsend, Manu V. Chakravarthy, and Clay F.
Semenkovich, of the Washington University School of Medicine, St.
Louis, MO, USA.