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Home | Pregnancy Timeline | News Alerts | News Archive June 28, 2013

 
Cellular reconstruction of mitochondrial DNA

Top: Cellular reconstruction of the mitochondrial network in mammalian cells
(labeled in grey) is shown. Complex I can be detected in red and complex IV in green.

Middle: The grey is removed and better detection of Complex I (red)
and complex IV (green) is appreciated.

Bottom: Yellow indicate co-localization of complex I and complex IV and
not co-localized complex I is red and not co-localized complex IV is green.

Credit: CNIC







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Spanish research creates a new model of mitochondrial function

This discovery confirms a model proposed by the same team in 2008. Observations made at that time could not be explained by the established model of mitochondrial function.

Mitochondria are the organelles in the interior of cells that extract energy from nutrients and convert it into a form that can be used by the cell.

The consumption, digestion and assimilation of nutrients serves the ultimate purpose of fueling each and every cell in the body. The breakdown of nutrients in the digestive tract requires energy to create simple compounds from larger components: glucose from sugars and carbohydrates, amino acids from proteins, and fatty acids from fat. These breakdown products enter cells and are processed by the mitochondria to release much larger quantities of energy.

Published in Science, this redefinition of mitochondrial function will require revision of all biochemistry textbooks

Dr. Jose Antonio Enríquez, lead investigator of the study: "Understanding how cells generate energy is fundamental to understanding living systems. For much of the last century, this has been the primary object of studies in biochemistry. By the beginning of the 80s the mystery of how mitochondria achieve this task was thought to be solved. In the 90s the molecular structures responsible were resolved in incredible detail. This had been considered to be one of the best understood processes in the cell."

This former view was overturned by the description of mitochondrial diseases. Despite the impressive accumulation of knowledge on mitochondrial function, the models could not explain the symptoms of these diseases, and researchers were unable to predict who would develop these diseases or how severe they would be, or explain their origin and mechanism. As a consequence, it has not been possible to develop effective treatments.

This situation revealed that our knowledge of mitochondrial function was much less complete than had been believed and that our models were inadequate. Therefore research over the last ten years has been directed at providing a better understanding of this process.

The new study confirms the model proposed in 2008 by the group led by Dr. Enríquez, who affirms that "this redefines our view of one of the most basic processes for life in all cells."


The energy released from ruptured chemical bonds in food molecules is temporarily stored as electrons in N and F molecules. By themselves, N and F cannot provide enough energy for the cell's needs. However, mitochondria use five molecular machines—known as complexes I, II, III, IV and V—to convert N and F stored energy into ATP. Until very recently these complexes were thought to float independently in the internal membrane of mitochondria, without interacting. Work by Dr. Enriquez's group has now shown this to be incorrect.


"The five complexes do not always move independently in the membrane," explains Dr. Enríquez. "On the contrary, they associate in distinct combinations called respriatory supercomplexes. Our work explains the functional consequences of these interactions."

The study shows that these associations are dynamic and are modified to optimize the extraction of energy from N and F molecules depending on their relative abundance, which in turn reflects the composition of foods consumed.

The Science study describes these supercomplexes and their functions. The significance of this according to Dr. Enriquez, is that "the system for optimizing the extraction of energy from food molecules is much more versitile than was believed and can be modulated in unexpected ways in order to adjust to the dietary composition of nutrients or to the specialized function of particular cell types."

During the study the team also made the unexpected discovery that the most widely used mouse strain for laboratory genetic analysis is unable to correctly assemble the respiratory supercomplexes. This raises serious questions about the validity of extrapolating results obtained with these mice to humans.

Original press release:http://www.eurekalert.org/pub_releases/2013-06/cndi-srr062513.php