We have previously discussed how there are variations within Mitochondrial DNA that can indicate athletic performance but that if the polymorphisms in the mitochondria (mtDNA) relating to elite performance in thoroughbreds existed, over the last 300 years we would have selected for it by now and all horses would come from the one, or two mitochondrial haplotypes. Humans haven’t been selected the same way as horses and there are a lot of different mitochondrial groups, even if we all go back to a mitochondrial eve at some point.
It is just as important to know that mitochondrial DNA is small in terms of size but does an awful lot in terms of function. How it does this is by using nuclear based genes to do the work. The limited coding capacity of mtDNA necessitates that nuclear genes make a major contribution to mitochondrial metabolic systems and molecular architecture. Consequently the vast majority of the mitochondrial proteins are nuclear-encoded and mitochondrial function depends on the coordinated expression of both nuclear and mitochondrial genomes through a process known as mitochondrial biogenesis. Basically, in order for the mitochondria to operate optimally, there is a nuclear-mtDNA "handshake" that takes place. Optimization of the process is just one aspect of mitochondrial function, the other is the actual number of mitochondria that exist on a per cell basis, the theory being, the more the merrier. It has previously been noted that the total amount of mitochondria in a given organism, as measured by whole body respiration, scales across organisms according to a power law of the body mass. Mitochondria abound in the heart, brown fat, and skeletal muscle, while mature red blood cells are devoid of mitochondria. Changes in energy demand and particular signaling events can modulate mitochondrial content.
A study released this week identified molecular probes and pathways that control mitochondrial abundance. After looking at literally thousands of molecules, the researchers found that only a few compounds deal with the relationship of mitochondrial content. They focused on one such compound, BRD6897, and demonstrated that it increases the cellular content of mitochondria however it does not appear to activate the known transcriptional programs of mitochondrial biogenesis, but rather, appears to influence mitochondrial content perhaps by modulating protein turnover. At present the precise molecular target (i.e the genes responsible for the creation) of BRD6897 remains a mystery, but if identified, could reveal an important new pathway, that together with transcriptional programs of mitochondrial biogenesis, would serve to regulate mitochondrial content.
So what does this mean for athletic performance in thoroughbreds? Right now, our understanding of the limits of athletic performance is that the 'first limiter' is delivery of oxygenated blood to the muscle, rather than mitochondria performance so in that respect, the cardiovascular capacity of the horse is a primary concern. However, when it comes to elite performance, the cardiovascular capacity is somewhat normalized in that in general all horses that are capable of consistent graded stakes performance have similar cardiovascular capacity. What separates them out at this point is their ability to deal with lactate and muscle fatigue. This is where optimal mitochondrial performance (biogenesis) and mitochondrial abundance should make a difference.