Functional Delivery of a Cytosolic tRNA into Mutant Mitochondria of Human Cells
Bidesh Mahata, Saikat Mukherjee, Sumita Mishra, Arun Bandyopadhyay, Samit Adhya
Science 20, October 2006: Vol. 314. no. 5798, pp. 471 - 474
Mitochondria, the energy producers within cells, contain their own DNA. Like DNA in the nucleus, mitochondrial DNA (mtDNA) can harbor mutations causing complex disorders, some of which affect the muscle and nervous system. Gene repair to correct these syndromes has been difficult because genetic material doesn’t readily enter human mitochondria. In a new study in Science, mitochondrial function is restored in mutant cells by using protein machinery from an unexpected source - a harmful parasite.
Parasites such as Leishmania can move RNA from the cytoplasm into their mitochondria. Scientists deduced that they must have proteins to specifically perform this function. With hopes of being able to eventually use this complex for treating human disorders, researchers from the Indian Institute of Chemical Biology in Calcutta, India, isolated the RNA Import Complex (RIC) from Leishmania.
In a further step towards this goal, Mahata and colleagues now apply RIC to diseased human cells. Human cells take up Leishmania RIC, which then triggers RNA transport. Then they test whether RIC helps cells overcome a defective mitochondrial tRNA gene that disrupts protein synthesis. RIC obligingly moves transfer RNAs (tRNAs) into mitochondria, which dramatically reverses the failure of protein production. In addition, RIC restores the respiratory (energy-generating) activity of the mutant mitochondria.
This study shows that Leishmania RIC protein complex has therapeutic potential for treating incurable syndromes caused by mitochondrial mutations.
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