S. Mukherjee, B. Mahata, B. Mahato, S. Adhya

Recent advances have highlighted the crucial role played by mitochondria in the etiology of a variety of rare maternally inherited disorders, in common complex diseases, as well as in normal physiological processes such as aging. One approach to the management of mitochondrial diseases would be to develop reagents to modulate mitochondrial function in vivo. Work in our laboratory is focused on the characterization of a multi-protein complex (the RNA Import Complex or RIC) from the kinetoplastid protozoon Leishmania tropica that transports tRNAs across mitochondrial membranes. The purified complex was efficiently taken up by human cells through a caveolin 1-depedent endocytotic pathway and targeted to mitochondria. The mitochondrial function of cybrid lines carrying the tRNA mutation that causes Myoclonic Epilepsy with Ragged Red Fibers (MERRF) was upregulated following administration of RIC. Conversely, RIC could be used to deliver signal-tagged antisense RNAs to mitochondria, resulting in degradation of the targeted mRNA and downregulation of respiration. This regime will be useful to study mitochondrial metabolism in cultured cells as well as in animal models.

Keywords (Optional): 
RNA delivery
protein complex