Metabolic implications for the mechanism of mitochondrial endosymbiosis and human hereditary disorders

The direct descendents of ancient, free-living bacteria can be found in the cells of animals and plants as mitochondria, and have a very important metabolic function. But how did independently existing bacteria come to be an integral part of every cell in the human body? The traditional view is that it was part of a mutually beneficial relationship between bacteria and their "host cells," with the bacteria gaining shelter and nutrients, and the host metabolizing energy more efficiently. Recent research suggests that the relationship might not have been so harmonious--that the host could be "farming" the bacteria, or that the bacteria could be little more than a parasite.

New models lend credence to the theory that cells do indeed farm the mitochondria with very tangible benefits in energy production. The result for the mitochondria is a lower growth rate within the cell. If the growth rate of mitochondria went unchecked, however, it would kill off the host cell. The limitation of growth helps keep the cell and the mitochondria alive.

Surprisingly, the limitation on the growth of mitochondria has profound implications for untreatable and often fatal diseases including Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis, and Stroke (MELAS) and Myoclonic Epilepsy with Ragged Red Fibers (MERRF). In these conditions, the mitochondria in human cells grow and reproduce unchecked, ultimately causing cells to rupture.

In such cases, cells mistakenly encourage growth and reproduction when they sense the presence of defective mitochondria--expending more and more energy that is needed for other cell functions. The result is the irreparable damage or even destruction of the host cell. The clear implication is that therapeutically blocking the cell proteins that mediate mitochondrial growth can help mitigate the negative--and potentially fatal--effects.