Souradip Mallick, National Institute of Technology, Rourkela
Inside mitochondria, there is a mitochondrial DNA which passed exclusively from mother to offspring through the egg cell. Mitochondrial DNA (mtDNA) evolves at a rapid rate than nuclear genetic markers, thus it plays a significant role in phylogenetics and evolutionary biology. It also regulates metabolism, epigenome modifications, and other processes vital for mammalian cell survival and activity. Mutations in mtDNA can impair the ETC by altering nuclear DNA (nDNA) co-evolved ETC complex protein interactions, causing defective respiration and debilitating diseases. The inability to edit mtDNA sequences creates difficulties for many studies and also its potential applications. Endonucleases targeted to the mitochondrion inefficiently eliminate and cannot alter mtDNA sequences.
A simple, high-throughput method was developed to transfer isolated mitochondria and also mitochondrial DNA into mammalian cells. This enables us to understand a key genetic component of cells and thus help to treat debilitating diseases such as cancer, diabetes, and metabolic disorders.
A device which was developed to transfer mtDNA is MitoPunch. By this device, mitochondria transfer into 100,000 or more recipient cells simultaneously, which significantly improves existing mitochondrial transfer technologies. The device helps to understand mutations in mitochondrial DNA by developing controlled, manipulative approaches, thus it improves the function of human cells or model human mitochondrial diseases better. It also helps potentially to develop disease models and regenerative therapies for disorders caused by mutations.
The MitoPunch device is very simple to operate and thus allow mitochondrial transfers from a wide range of mitochondria isolated from different donor cell types into a multitude of recipient cell types, even for non-human species.
This new technology is significantly different from other technologies because of its ability to engineer non-immortal, non-malignant cells like human skin cells, to generate unique mitochondrial DNA-nuclear genome combinations. These techniques help to study the impact of specific mitochondrial DNA sequences on cell functions by enabling the reprogramming of these cells into induced pluripotent stem cells that were then differentiated into functioning fat, cartilage, and bone cells.
MitoPunch is a photothermal nanoblade whose primary principle is to use pressure to propel an isolated mitochondrial suspension through a porous membrane coated with cells. This applied pressure gradient puncture cell membranes at discrete locations, allowing the mitochondria direct entry into recipient cells, followed by cell membrane repair.
This new device is very efficient and thus it helps to study the mitochondrial genome more simply — swapping it from one cell into another — which can be used to uncover the basic biology that governs a broad range of cell functions and could, one day, offer hope for treating mitochondrial DNA diseases.
Also read:BRAIN FOG: A temporary post-COVID-19 brain disorder
Source:Pressure-driven Mitochondrial Transfer Pipeline Generates Mammalian Cells of Desired Genetic Combinations and Fates by Alexander N. Patananan et al, December 11,2020 DOI:10.1016/j.celrep.2020.108562
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