Investigating the Quality Control of Mitochondria
Mitochondria are the power plants of your cells, and are very important in degenerative aging. Differences in mitochondrial structure correlate strongly with differences in species life span, and there is every reason to believe that accumulated damage to mitochondria plays a large part in the destruction of health and vigor that comes with age.
We know that mechanisms like autophagy exist within a cell to recycle damaged mitochondria: these mechanisms are just not effective enough to prevent the forms of damage that contribute to aging. But do mitochondria repair themselves? The distant ancestors of mitochondria were free-living bacteria, so it might not be unreasonable to expect them to be at least partly capable of self-repair. If natural mechanisms of mitochondrial repair can be identified, then potentially better repair and rejuvenation biotechnologies could arise from that knowledge. Clearly whatever mechanisms exist are not good enough to keep us from degenerating, but we clever humans should be able to greatly improve upon the basic model.
The research community is not lacking in means to deal with mitochondrial damage, of course - there are at least four or five potential paths ahead, such as replacing mitochondrial DNA throughout the body or moving the most important mitochondrial genes into the cell nucleus. But the more the merrier: twenty lines of research are far more likely to produce a meaningful result sooner and more effectively than five.
I looked at mechanisms of repair in mitochondria a few years back, a post largely focused on DNA repair. For today we'll look at a different aspect of repair, the removal of damaged molecules that degrade the effectiveness of cellular machinery. I'm going to direct your attention to a pair of papers that propose that mitochondria maintain an internal mechanism of quality control that is separate from - but very similar to and influenced by - the housekeeping processes of the cell itself.
The accumulation of unhealthy mitochondria results in mitochondrial dysfunction, which has been implicated in aging, cancer, and a variety of degenerative diseases. However, the mechanism by which mitochondrial quality is regulated remains unclear. Here, we show that Mieap, a novel p53-inducible protein, induces intramitochondrial lysosome-like organella that plays a critical role in mitochondrial quality control.
Maintenance of healthy mitochondria prevents aging, cancer, and a variety of degenerative diseases that are due to the result of defective mitochondrial quality control (MQC). Recently, we discovered a novel mechanism for MQC, in which Mieap induces intramitochondrial lysosome-like organella that plays a critical role in the elimination of oxidized mitochondrial proteins ... However, a large part of the mechanisms for MQC remains unknown. Here, we report additional mechanisms for Mieap-regulated MQC.
The really fascinating thing here, for those of you following along at home, is the involvement of p53, a protein cog in the cellular machinery that seems to have its thumb firmly stuck into every pie when it comes to aging, cancer, and all related topics. At least one method of extending healthy and maximum life span in mice involves alterations to p53, and no doubt more will follow.
The larger and more complex neurons of larger animals are said to require even vaster amounts of energy to keep functioning even while in a resting state. Giraffe and Whales have extraordinarily large motorneurons. And while it is true that more than half can fail through time in an aging body, a substantial percentage seems to keep on going, particularly in some species of whales for over two centuries. These are permanent nondividing cells of extreme metabolic activity.
Some studies suggest they can even export garbage such as lipofuscin outside themselves and probably outside the brain itself.
That there is an existing mechanism to rejuvenate mitochondrial populations is all but certain. The question is what is it, and why does it fail in a substantial portion of the neural population