Thursday, 26 January 2012

Untidy Houseguests: How Our Bacterial Powerhouses Might Be Slowly Killing Us

"When our ancient eukaryotic ancestors decided to take in bacterial boarders, it seemed like a pretty good deal, as they were good at stoking the furnaces. Alas, they did not foresee the possibility that these creatures, which became our mitochondria, might also create some household problems." - George M. Martin, "The biology of aging: 1985-2010 and beyond"

The opening quote is a line from a really good review of aging which I heartily recommend. I also included it because it's actually a good way of introducing the concept of mitochondria.

Meet your (literal) fuel cells
 The leading theory on the origin of mitochondria is that at some point in evolutionary history, a bacteria was absorbed into a larger cell, and survived the process. The bacteria then became a part of the larger cell because it allowed an evolutionary advantage of providing energy to the cell, in a process which I'll now explain.

As you can see in the image above, mitochondria have a quite complex construction. As with many cells, mitochondria have an inner membrane, an outer membrane, and a gap between the two referred to as the intermembrane space. The lines you can see stretching across the mitochondrion are infoldings of the inner membrane, and are called cristae. The area inside of the mitchondrion is called the matrix. The small black circles are granules, which aren't particularly involved in the energy process.

As we all know, when eat food, our stomachs break it down into more basic parts through digestion. But where do these parts go? Glucose, which is a simple sugar, moves into the glycolysis pathway. This involves several different enxymes breaking down and altering glucose into a number of different forms until it becomes yet another molecule, acetyl Coenzyme A, which is commonly referred to as acteyl CoA. This molecule then moves into a new cycle called the Citric Acid Cycle, which takes place in the matrix of the mitochondria.

 As you can see, this cycle takes in the acetyl CoA molecule and uses it to convert many compounds into high energy compounds, such as ATP and NADH. These compounds are then used throughout the body as a sort of energy currency, fuelling the various processes needed to keep you alive. 

Unfortunately, this process isn't perfect. An unwanted by-product of this process is the release of electrons. Normally, the mitochondria can reabsorb these electrons to be used in different cycles, but occasionally they can be leaked out into the cell. The result is the formation of reactive oxygen species. These molecules can cause serious damage to both the DNA of mitochondria and the cells of the body, which can lead to mutations. These mutations can lead to further leakage of electrons and this leads to further... You see where we're going with this.

So are our fuel cells to blame for ageing as we know it? Hard to say. The electrons that initially leak out tend to be the result of mutations in the DNA, which can occur randomly over time. However, mitochondrial ageing could actually be a RESULT of a different theory of ageing. What if, for instance, the decay of telomeres discussed in the previous post caused the mitochondrial leakage? What if it is something else entirely? It is difficult to say whether the damage of free radicals is a cause or effect of ageing.

You'd be amazed at how often that happens in Biology.

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