Mitochondria have their own DNA, but the 13 genes in human mitochondria – along with DNA sequences for tRNAs, rRNAs and some small peptides – are massively overshadowed by the 20,000 genes in the human nucleus. However, these diminutive mitochondria may have a strong influence on cellular metabolism and susceptibility to metabolic diseases like heart failure or obesity.
About 1.5 billion years ago, tiny visitors came to live inside the cells that later evolved into all plant and animal life – including humans. Those who were mitochondria, small organelles whose prominent role is producing 90 percent of the chemical energy cells need to survive. Evolutionarily speaking, humans, animals and plants are thus a combination of two organisms.
Mitochondria have their own DNA, but the 13 genes in human mitochondria – along with DNA sequences for tRNAs, rRNAs and some small peptides – are massively overshadowed by the 20,000 genes in the human nucleus. Nevertheless, these diminutive mitochondria may have a strong influence on cellular metabolism and susceptibility to metabolic diseases like heart failure or obesity, according to Scott Ballinger.
"For 50 years," Ballinger said, speaking about studies of the chromosomal genes in the cell nucleus. "But this explains only 10 percent of the reasons for susceptibility to disease." The possible impact of mitochondrial DNA on disease susceptibility depends on two facts. First, all of a person's mitochondrial DNA comes from the mother, via her egg. This is distinct from the chromosomal genes in the nucleus, where, on average, half comes from the mother and half from the father.
Second, human mitochondrial DNA has evolved into distinct haplotypes, and each of these types has mitochondrial DNA variations that are inherited together. There are approximately 25 to 35 basic mitochondrial DNA haplogroups, and one of them – found in African populations – has many subtypes due to the deep genetic diversity of that continent.
To investigate the impact of mitochondrial DNA, Ballinger and colleagues looked for changes in metabolism and nuclear gene expression when they exchanged mitochondrial backgrounds of strains of mice – those having different mitochondrial DNA sequences, and also having remarkable differences in susceptibility to diseases associated with metabolism.
After switching the mitochondrial DNA, Ballinger and colleagues measured changes in body composition, metabolism and nuclear gene expression in fat tissue when mice switched from a low-fat diet to a high-fat diet.
In the first report of its kind, they found that switching the mitochondrial genetic background had a significant impact on adiposity, whole body metabolism and nuclear gene expression in mice.
"These results are clearly consistent with the notion that different nuclear-mitochondrial genetic combinations influence metabolism, adiposity and gene expression in different ways," Ballinger said.
"The overall implication of this work is that it can provide a new framework for understanding complex genetic disease susceptibility – that both individual and nuclear mitochondrial, in combination, can affect disease development. of nuclear and mitochondrial encoded genes interact to alter metabolism, and how this influences individual disease susceptibility. "