Freitag, 18. September 2015

Mitochondrial Deletions Matter in the Heart: another mosaic piece gets us closer to a solution

Here, I will discuss a recent paper by Baris, ..., Wiesner et al. (1). This work is from a Cologne group and the renowned “Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD)”.

In the discussion the authors describe their hypothesis thusly:
Tissues of aged mammals display respiratory mosaicism, i.e., few cells with severe mitochondrial dysfunction embedded into normal tissue. This was shown for heart, skeletal muscle of the limbs and extraocular muscle, substantia nigra, and liver (reviewed in Larsson, 2010). However, it was unclear whether this mosaic phenotype is responsible for causing any of the typical aging-related symptoms of organ dysfunction.

Of course, the interested reader will note that it was not at all "unclear". The evidence is certainly controversial, particularly in humans/Rhesus monkeys, but by no means non-existent. I am not a fan of overselling and plenty of data by Aiken-McKenzie and others supports the idea (c.f. ref. 3 and start from there). One should give credit when it’s due, which is what the editorial by Khrapko et al. does (2). The paper by Baris et al. while interesting is certainly not any more definitive than the data we already have. However, it does clarify some controversy surrounding the TWINKLE KO model of accelerated deletion accumulation.