Day 076 - Mitochondrial bomb-shelters

Submitted by Sam on 5 August, 2011 - 01:06

Our cells generate most of the energy they need in tiny structures inside them called mitochondria, which can be thought of as the cells' powerhouses. Mitochondria have their own DNA, independent of the cell's nuclear genome, which is compelling similar to the DNA of bacterial genomes. What this suggests is that many thousands of years ago, mitochondria were not just components of our cells, but were in fact unicellular organisms in their own right. According to this hypothesis – the endosymbiotic theory – mitochondria (and possibly some other organelles) originated as free-living bacteria which later became incorporated inside other cells in a symbiotic relationship.

Like man-made powerhouses, mitochondria produce hazardous by-products as well as useful energy. They are the main source of free radicals in the body – hugely reactive particles which cause damage to all cellular components through oxidative stress. They attack the first thing they come across, which is usually the mitochondrion itself. This hazardous environment has put the genes located in the mitochondrion at risk of mutational damage, and over many years of evolutionary pressure the mitochondrial DNA has gradually moved into the cell's nucleus, where it is comparatively well-protected from the deleterious effects of free-radicals alongside all of the cell's other DNA. This is called allotopic expression, and it has moved all but thirteen of the mitochondrion's full complement of at least one thousand genetic instructions for proteins into the 'bomb-shelter' of the nucleus.

However, the remaining thirteen genes in the mitochondrion itself are subject to the ravages of free-radicals, and are likely to mutate. Mutated mitochondria, as Aubrey de Grey has identified, may indirectly accelerate many aspects of ageing, not least when their mutation causes them to no longer produce the required energy for the cell, in turn impairing the cell's functionality. In order to combat the down-stream ageing damage as a consequence of mitochondrial mutation, de Grey believes that the mitochondrial DNA damage itself needs to be repaired or rendered harmless.

His characteristically bold solution to this problem is to put the mutations themselves beyond use by creating backup copies of the remaining mitochondrial genetic material and storing them in the safety of the cell's nucleus. Allotopically expressed here, like the rest of the mitochondrial DNA, any deletions in the mitochondrial DNA can be safely overwritten by the backup master copy, which is much less likely to mutate hidden away from the constant bombardment of free radicals. There are several difficulties to this solution, not least the fact that the remaining proteins are extremely hydrophobic and so don't 'want' to be moved at all, and additionally the code disparity between the language of the mitochondrial DNA and the nuclear DNA which makes a simple transplantation without translation impossible.

Even if this engineered solution to the problem proves impracticable, at the very least the theory is sound. If we can devise a way systematically defend our mitochondria from their own waste products, we will drastically reduce the number of harmful free radicals exported throughout our bodies, thereby reducing preventing a lot of the damage that distinguishes the young from the old, extending and improving the quality of our lives as a result.

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