A New Study Uncovers the Importance of Mitochondrial Fusion

Mitochondria are aptly deemed the "powerhouses of the cell." Through the process of oxidative phosphorylation they generate adenosine triphosphate (ATP), which provides the energy to run a vast number of cellular processes. ATP provides the cellular energy we need to perform a wide variety of ordinary daily tasks, such as providing fuel to our muscles to get out of bed, to walk, to keep our heart beating, and to maintain breathing.

While the production of ATP and its use sounds simple enough and mitochondria are often described as autonomous cellular organelles; mitochondria are actually regulated by a complex series of events in which they fuse with one another and divide throughout a cell. Although varying ideas have been postulated on the purpose of this dynamic process, a new study published in the journal Cell was designed to understand the physiological role of this function in an intact organism.

The authors deleted genes in mice which had previously been demonstrated to prevent mitochondrial fusion. Specifically, the fusion genes Mfn1 and Mfn2 were conditionally deleted in skeletal muscle. The authors use the cre-lox system and place cre recombinase downstream of the MLC1f promoter, which is only activated in skeletal muscle and placed lox sites surrounding the noted fusion genes.

Interestingly, mice with both genes deleted are blunted in size, have altered body temperature, reduced blood glucose levels, and increased serum lactate levels. The authors suggest that reduced glucose and increased lactate are due to the loss of efficient oxidative phosphorylation. That is, a heavy use of glycolysis instead of oxidative phosphorylation to produce ATP. Consistent with this result, cells lacking the fusion genes consume less oxygen and produce little ATP compared to wild type cells.

The authors also observed a decrease in the overall size of skeletal muscle, a reduced amount of mitochondrial DNA (mtDNA) present in cells, and an increase in mtDNA mutations. This suggests that fusion is not only important for mitochondrial fidelity and function, but for proper muscle development.

This work is significant in that it demonstrates a physiological function for mitochondrial fusion in development and metabolism using an intact animal. The study may also have implications for understanding mitochondrial diseases in humans, and although a long way off, suggests that fusion may be a therapeutic avenue to address in the future.

References:

Chen H, Vermulst M, Wang YE, Chomyn A, Prolla TA, McCaffery JM, Chan DC. Mitochondrial Fusion Is Required for mtDNA Stability in Skeletal Muscle and Tolerance of mtDNA Mutations. Cell. 2010 Apr 16;141(2):280-9.