New mitochondria study could pave way for disease treatments

November 17, 2022 - 3 minutes
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Mitochondria, the ‘powerhouses of the cell,’ are important cellular structures that are vital for their role of generating energy. 

They constantly fuse together and split apart. They contain a small amount of genetic information, mitochondrial DNA (mtDNA). The mtDNA, organized into dot-like structures called nucleoids, also moves around inside the mitochondria. The method of distribution of mtDNA remained unclear. Now a research team led by Osaka University in Japan has identified the molecule ATAD3A, which is essential for nucleoid movement.

The discovery could be a potential therapeutic candidate for mitochondrial diseases.

The team previously showed movement of nucleoids is linked to the fission of mitochondria. However, the mechanisms and function of this movement were unclear. The researchers studied the role of ATAD3A in nucleoid movement because of its previously established links to nucleoid formation.

In the Proceedings of the National Academy of Sciences, the researchers showed that ATAD3A, which is anchored to the inner mitochondrial membrane, mediated the interaction of mtDNA nucleoids (present inside the mitochondria) with factors involved in mitochondrial fission (present on the outer mitochondrial membrane).

They demonstrated that ATAD3A was essential for the active movement of mtDNA nucleoids within the mitochondria—a process called nucleoid trafficking—and that nucleoids were abnormally clustered in cells that lack mitochondrial fission. Together, mitochondrial fission and nucleoid trafficking determine the size, number, and distribution of the nucleoids within the mitochondria.

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Respiratory chain complex

The distribution of nucleoids throughout the mitochondrial network activates expression of the mtDNA and increases formation of the respiratory chain complex. This is a group of several proteins essential for energy production within cells, and the correct distribution of the mtDNA nucleoids is key for efficient energy production. 

“Regulation of nucleoid dynamics is crucial for the maintenance of respiratory chain complexes on the mitochondrial inner membrane, and this is the first report of the role of ATAD3A in mitochondrial nucleoid dynamics,” said lead author Takaya Ishihara. 

This mitochondria study provides scope for future therapies

The development of techniques to alter mtDNA movement may help regulate mitochondrial function in the future. 

“Nucleoid trafficking may represent a new therapeutic target to prevent mitochondrial dysfunction in various human diseases,” added senior author Naotada Ishihara.

The researchers said that not only does this new study increase knowledge of the regulatory processes in mitochondria but it also provides scope for developing future therapies against abnormal mitochondrial functioning.

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