Methodology can significantly assist scientists in better understanding mitochondrial diseases.
UCLA School of Medicine researchers have developed a systematic method of moving mitochondria and its related DNA into cells.
This method helps researchers to study how one part of a cell functions to treat diseases like cancer, diabetes and metabolic disorders.
A research published online in the journal Cell Reports explains how the current UCLA-developed technique builds upon and improves a previous mitochondrial transfer technique.
The system is part of a UCLA research program to better understand mitochondrial DNA mutations by creating a controlled approach to manipulating human cells.
The ability to produce cells with a SLO and desired mitochondrial DNA sequences has great potential for researching how genomes in mitochondria and the nucleus interact to control cell function, which could be important for understanding and possibly treating disease in patients.
Mitochondria are born from the female and are thus inherited from that person’s mother.
The mitochondria depend on the integrity of their mitochondrial DNA to do their essential functions.
Mitochondrial DNA mutations can dramatically impair mitochondria energy output, leading to life-threatening and debilitating diseases.
Technologies for manipulating mitochondrial DNA is behind developments in manipulating DNA in the nucleus. These technologies can help researchers create disease models and regenerative therapies for genetic diseases.
However, existing methods have limitations and consist mainly of complex protocols for integrating mitochondria with desired mitochondrial DNA sequences into a small and a narrow variety of cells.
The MitoPunch system is easy to use for in vivo transfer of mitochondrial DNA from a diverse range of mitochondria into a variety of recipients, including for non-human species.
“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,” said co-first author Alexander Patananan, a UCLA postdoctoral fellow now at Amgen. “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 established in the laboratories of Dr. Michael Teitell of the Jonsson Cancer Center and professor of pathology and laboratory medicine of UCLA’s Henry Samueli School of Engineering and Applied Science, and Dr. Pei-Yu Chiou of the UCLA Mechanical and Aerospace Engineering Department.
MitoPunch is the next step in the research team’s previous technology and system called the photothermal nanoblades.
However, unlike the photothermal nanoblade, which involves sophisticated lasers and optical systems to operate, MitoPunch works by using pressure to move a biologically isolated mitochondria through a porous membrane coated with cell membranes.
The research suggests that this applied pressure gradient enables mitochondria to penetrate the envelopes of recipient cells directly, accompanied by the membrane repair of the membrane.
“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. “The new device allows researchers to study the mitochondrial genome to their heart’s content”