New insights into mitochondrial nucleotic dynamics

Mitochondria, known as the power source of cells, are important cellular structures that are essential
for their role in producing energy.
Mitochondria are "dynamic," meaning they are constantly fusing and dividing
.
They contain small amounts of genetic information
called mitochondrial DNA (mtDNA).
Mitochondrial DNA is organized into dot-like structures called "nucleoids" that also move
within the mitochondria.
The distribution method of mtDNA is unknown, but now a team led by Osaka University has discovered a molecule called ATAD3A, which is essential for nucleoidal movement and could be a potential therapeutic candidate for mitochondrial diseases
.

The team has previously demonstrated that the movement of nucleoids is associated
with the fission of mitochondria.
However, the mechanism and function of this movement are unclear
.
Therefore, the researchers investigated the role of ATAD3A in the nucleoid-like movement, as it had previously established a link
to the formation of the nucleoid.

The researchers found that ATAD3A, fixed on the inner mitochondrial membrane, mediates the interaction
between mtDNA nuclei, which is present within the mitochondria, and factors involved in mitochondrial fission (present on the outer mitochondrial membrane).
They demonstrated that ATAD3A is essential for active movement of mtDNA nucleioid within mitochondria — a process known as nucleoid "transport" — and that nucleoids aggregate
abnormally in cells lacking mitochondrial fission.
Mitochondrial fission and nucleoid transport together determine the size, number, and distribution
of nucleoids within mitochondria.

The distribution of nucleioid in the mitochondrial network activates the expression of mtDNA, increasing the formation of the "respiratory chain complex", a group of proteins necessary for energy production within cells, and the correct distribution of mtDNA nucleoids is key
to efficient energy production.
"Regulation of nucleoidal dynamics is critical for the maintenance of respiratory chain complexes on the inner mitochondrial membrane," explains first author Takaya Ishihara, "This is the first report
on the role of ATAD3A in mitochondrial nucleoid dynamics.
" ”

The development of techniques that alter mtDNA movement may help regulate mitochondrial function
in the future.
Senior author Naotada Ishihara explains: "Nucleoidal transport may be a new therapeutic target for the prevention of mitochondrial dysfunction in various human diseases
.
" Thus, this work not only increases our understanding of mitochondrial regulatory processes, but also provides space
for the development of future therapies targeting mitochondrial dysfunction.

Mitochondrial nucleoid trafficking regulated by the inner-membrane AAA-ATPase ATAD3A modulates respiratory complex formation