Synchronizing mitochondrial metabolism

October 22, 2014 § Leave a comment

Seeing mitochondria go through waves of ATP production. Image by Roberto Weigert and Natalie Porat-Shliom.

Watching mitochondria go through waves of ATP production. Image by Roberto Weigert and Natalie Porat-Shliom.

Mitochondria are fidgeters. That’s what researchers discovered in a recent study. The organelles undergo waves in ATP production. Furthermore, the mitochondria, like synchronized dancers, work in a coordinated fashion.

A team at the National Institute of Dental and Craniofacial Research report in a paper just out in the journal Cell Reports that mitochondria in the salivary glands of live rats “undergo sustained and spontaneous metabolic oscillations under basal conditions,” says Roberto Weigert, who led the study. “Although we do not know why mitochondria adopt this oscillatory modality, we have speculated that this is the best way to rapidly respond to changes in energy demands.”

Weigert explains that the oscillations refer to periodic oscillations in ATP production. “When you image the mitochondria, it gives the impressions of a movement, but in reality they are physically steady,” he says.

The finding that mitochondria undergo oscillations in ATP production contradicts earlier reports that the phenomenon occurred only when cells in culture were stimulated. But Weigert and colleagues found that mitochondria in the acinar cells in the salivary tissues oscillate their energy output without any trigger for as long as tens of seconds to minutes. The oscillations were longer, faster and more frequent than observed previously in cell culture.

Furthermore, the investigators found that mitochondria synchronized their energy output throughout the entire tissue by relying on the activity of gap junctions.  “It was a real surprise to observe large areas of the salivary tissue ‘oscillating’ in a coordinated fashion,” says Weigert. “Our study underscores the role of the tissue environment in regulating and coordinating basic cellular processes in ways that are different from what is observed in reductionist model systems.”

To study mitochondria in tissues of live rodents, the investigators used a technique called subcellular intravital microscopy. The technique gave a readout of NADH, which is the substrate of complex I during oxidative phosphorylation in mitochondria, and TMRM, a cationic dye that shows the mitochondrial membrane potential.

Through other experiments, the investigators found that the metabolic oscillations were connected to the production of reactive oxygen species, which are a byproduct of ATP production in mitochondria.  The observation hints that the oscillations reflect the energy status of the cells.

Weigert says the team now is “interested in characterizing the machinery initiating and regulating the oscillations in the salivary glands.” He adds they want to extend their studies to other organs in order to establish how widespread is the process and to find how the oscillations are altered during high-energy processes or pathological conditions, such as cancer or metabolic diseases.

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