Mitochondrial transfer
A group of researchers from the Johnson Cancer Center at the University of California, Los Angeles has developed a simple and high-performance method for transferring isolated mitochondria and mitochondrial DNA into mammalian cells. It allows you to adapt the genetic component of cells, making it possible to study and treat oncological diseases, diabetes mellitus, metabolic disorders.
A new study published in the journal Cell Reports describes a MitoPunch device that transfers mitochondria to 100,000 or more recipient cells simultaneously, which is a significant improvement over existing mitochondrial transfer technologies. This device was developed as part of the ongoing work of the University of California to study mutations in mitochondrial DNA by creating methods for controlled manipulations that improve the function of human cells or simulate mitochondrial diseases.
The ability to generate cells with the desired mitochondrial DNA sequences is very important for studying how genes in the mitochondria and nucleus interact in the process of regulating cell functions.
Mitochondria are inherited through the maternal line. Inherited or acquired mutations of mitochondrial DNA can significantly reduce energy production and lead to chronic diseases. Mitochondrial DNA manipulation technologies help scientists develop disease models and treatments for disorders caused by these mutations.
Mitochondrial DNA manipulation capabilities lag behind advances in nuclear DNA manipulation. Existing technologies are limited, complex, and can deliver mitochondria with desired mitochondrial DNA sequences only to a limited number of cells.
The MitoPunch device is easy to operate and provides simultaneous transfer of mitochondrial DNA from different types of donor cells to many types of recipient cells, including cells isolated from mice.
What distinguishes MitoPunch from other technologies is the ability to design living non-malignant cells, such as human skin cells, to create unique combinations of mitochondrial DNA and the nuclear genome. This progress made it possible to study the effect of specific mitochondrial DNA sequences on cell functions, as well as to reprogram them into induced pluripotent stem cells, which then differentiated into functioning cells of adipose, cartilage and bone tissue.
MitoPunch is based on the previous technology of photothermal nanoleather, which the group developed in 2016. Unlike photothermal nanoswitch, which requires sophisticated lasers and optical systems to operate, MitoPunch uses pressure to propel an isolated mitochondrial suspension through a porous cell membrane. The researchers suggest that this pressure gradient creates the ability to pierce the membrane of recipient cells in certain areas, allowing mitochondria to directly penetrate inside, followed by the restoration of the cell envelope.
Thus, the new device is more efficient than its predecessors, it allows researchers to study the mitochondrial genome by moving it from one cell to another. The authors hope that MitoPunch will help develop a treatment for diseases associated with mitochondrial DNA mutations.
Article by A.N.Patananan et al. Pressure-Driven Mitochondrial Transfer Pipeline Generates Mammalian Cells of Desired Genetic Combinations and Fates published in the journal Cell Reports.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on UCLA Jonsson Comprehensive Cancer Center: UCLA scientists develop high-throughput mitochondria transfer device.