The mitochondrion is a machine within the cell that does the chemistry of breathing. That is, it takes oxygen and chemically combines it with energy-rich nutrients from our food, to make carbon dioxide and water (which we exhale) and ATP, the "energy currency" of the cell.

The mitochondrion is therefore a really essential part of the cell. Lots of other parts of the cell are essential too, though, so why have a whole SENS page on it? The answer is: unlike any other part of the cell, mitochondria have their own DNA. This means that they can stop working as a result of mutations. Because the DNA is in a different place than the rest of the cell's DNA (which is in the nucleus), we need a different system to combat the inevitable accumulation of such mutations.

As usual, we're lucky - evolution has done the hardest part of this for us already. Mitochondria are very complex -- there are about 1000 different proteins in them, each encoded by a different gene. But nearly all of those genes are not in the mitochondrion's DNA at all! -- they are in the nucleus. The proteins are constructed in the cell, outside the mitochondrion, just like all non-mitochondrial proteins. Then, a complicated apparatus called the TIM/TOM complex (no kidding...) hauls the proteins into the mitochondrion, through the membranes that make its surface. Only 13 of the mitochondrion's component proteins are encoded by its own DNA.

This gives us a wonderful opportunity: rather than fixing mitochondrial mutations, we can obviate them. We can make copies of those 13 genes, modified in fairly obvious ways so that the TIM/TOM machinery will work on them, and put these copies into the chromosomes in the nucleus. Then, if and when the mitochondrial DNA gets mutated so that one or more of the 13 proteins are no longer being synthesised inside the mitochondria, it won't matter -- the mitochondria will be getting the same proteins from outside. Since genes in our chromosomes are very, very much better protected from mutations than the mitochondrial DNA is, we can rely on the chromosomal copies carrying on working in very nearly all our cells for much longer than a currently normal lifetime.

The cells that most severely accumulate mutant mitochondria are non-dividing ones like muscle fibres and neurons. This is a shame, because it means we will need really good gene therapy to get these supplementary genes into the cells that need them. But gene therapy is improving all the time - and also, even if we could only fix half the affected cells, we'd still be achieving a rejuvenation, which we could progressively improve upon with new gene therapy advances.

This project needs a lot of work over and above improvements in gene therapy technology, though, even though it sounds simple. The 13 proteins of interest are actually quite difficult for the TIM/TOM machinery to process even when we "tell" it to do so, so we still need to work on making that part easier. But there has been good progress in this area in the past few years.

Talks on this topic at IABG 10:
King

Talks on this topic at SENS2:
Weiner      Lightowlers      Yagi      Smigrodzki