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


Cite as:

Benjamin Lovegren de Bivort, Chun-Chung Chen, Fabrizio Perretti, Giacomo Negro, Thomas M. Philip and Yaneer Bar-Yam, Metabolic implications for the mechanism of mitochondrial endosymbiosis and human hereditary disorders. Journal of Theoretical Biology, 2007.


Summary

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.


Press Release

Researchers shed light on evolutionary origins of mitochondria

Cambridge, MA--Scientists at The New England Complex Systems Institute (NECSI) have used mathematical models to help elucidate the origins of mitochondria, the parts of a cell that use oxygen to generate cellular energy from carbohydrate molecules. Because mitochondria have their own genomes, it's commonly agreed that they were once free-living organisms. Though it is unclear exactly how mitochondria adopted the role they currently play in cells, NECSI researchers have moved closer to understanding this process in an article forthcoming from The Journal of Theoretical Biology.

"The process by which free-living bacteria first came to reside within host cells is called endosymbiosis," said Benjamin Lovegren de Bivort, a researcher at NECSI and Harvard University. "The traditional view of this progression is that endosymbiosis benefited both the mitochondrial ancestor and the host cell, the mitochondria receiving shelter and nutrients, while the host received efficient energy metabolism. However, according to our study, this isn't necessarily the case."

By modeling the transfer of metabolic nutrients between host cells and mitochondria, NECSI found strong support for the idea that mitochondria benefited significantly less from the combination than their host cells.

"In our models the mitochondria demonstrated a lower rate of growth after symbiosis than before," said Dr. Yaneer Bar-Yam, president of NECSI. "This means that endosymbiosis wasn't mutually beneficial, but rather that the host cells may have 'farmed' the mitochondria for their metabolic abilities."

According to the researchers, the reduction in growth rate is due to the requirement that the mitochondria are contained by and cannot reproduce more quickly than their hosts.

"Though it might be in the short-term interest of mitochondria to reproduce as quickly as possible in their host cells," said Bivort. "This kind of over-reproduction could also kill the cell, resulting in the death of the symbiotic mitochondria as well."

Surprisingly, this information may hold the key to dealing with mitochondria-related diseases such as Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis, and Stroke (MELAS) and Myoclonic Epilepsy with Ragged Red Fibers (MERRF). These fatal illnesses result from the over-production of mitochondria, and might one day be treated by blocking the proteins that cause this proliferation.


The New England Complex Systems Institute (NECSI) is an independent non-profit dedicated to promoting the science of complex systems, the mathematical study of how parts of a system give rise to its collective behaviors. Based in Cambridge, MA, NECSI coordinates original research, education, and community development that applies the study of complex systems to the advancement of science and the improvement of our society. To find out more, visit www.necsi.org.

 

 

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