Scientists at the Jonsson Cancer Center have developed a simple method to transfer mitochondrial DNA and mitochondria into cells. This method allows researchers to genetically modify a crucial genetic component to study how cells function, with the aim of potentially curing crippling diseases.
A research published today in the Cell Reports journal explains how the latest UCLA-developed technology, called Mitotransfer, moves mitochondria into 100,000 or more recipient cells, a major improvement over current tissue transfer technologies. The device is part of an ongoing project by UCLA scientists to recognize mitochondrial DNA mutations by creating a method to monitor mitochondrial DNA.
Mitochondria, which are considered the powerhouse of the cell, are inherited from a person’s mother. Mitochondria rely on the integrity of their DNA to perform their basic cellular functions. Genetic mutations in the mitochondria can disrupt energy production leading to serious diseases.
Technologies for editing the mitochondrial genome lag behind current developments for editing the genome in the nucleus, which could help scientists build models and therapies for mitochondrial diseases. However, previous methods have been limited and slow, and for the most part currently only work with a limited and diverse number of cells.
The MitoPunch system is used to reliably transfer mitochondrial DNA from a variety of different mitochondria to a variety of different recipient cell types, including cells from mice.
“What sets MitoPunch apart from other technologies is the ability to manipulate non-immortal, non-malignant cells such as human skin cells to generate unique combinations of mitochondrial DNA and nuclear genome,” claimed co-first author Alexander Patananan, a UCLA postdoctoral fellow. “This advance allowed us to study the effects of specific mitochondrial DNA sequences on cell function by also enabling the reprogramming of these cells into induced pluripotent stem cells, which were then differentiated into functioning fat, cartilage and bone cells.”
MitoPunch was developed in the laboratories of Michael Teitell, M.D., director of the Jonsson Cancer Center and professor of pathology and laboratory medicine; Pei-Yu (Eric) Chiou, professor of mechanical and aerospace engineering at the UCLA Henry Samueli School of Engineering and Applied Science; and Ting-Hsiang Wu of ImmunityBio, Inc.
The mitoPunch device builds on the earlier optical nanobender that our team built in 2016. Unlike other nanobreakers, MitoPunch does not use lasers or optical devices, but instead uses pressure to move an isolated mitochondrial suspension through a porous membrane coated with cells. The researchers assume that this applied pressure gradient allows the ability to penetrate mitochondria directly to repair cell membranes, followed by the organization of new membranes.
“We knew when we first developed the photothermal nanoblade that we needed a higher-throughput system that was easier to use and easier for other labs to assemble and operate,” said Teitell, who is also chief of the Division of Pediatric and Developmental Pathology and a member of the UCLA Large Stem Cell Research Center. “This new device is very efficient and allows researchers to easily study the mitochondrial genome – swapping it from one cell to another – which can be used to uncover the basic biology that controls a wide range of cellular functions and could one day offer hope for treating diseases involving mitochondrial DNA.”.