Targeting the mitochondrial genome through a nanocarrier and the regulation of mitochondrial gene expression

Abstract

Mitochondria are attractive organelles that have the potential to contribute greatly to medical therapy. This organnelle is responsible for a variety of essential functions including ATP production and the regulation of apoptosis, and they have their own genome, mitochondrial DNA (mtDNA). It has recently become evident that a variety of human diseases are associated with mitochondrial dysfunctions caused by mutations and defects in mtDNA. Therefore, the ability to successfully target the mitochondrial genome and to regulate mitochondrial gene expression would contribute to mitochondrial gene therapy for various human diseases. To achieve such an innovative objective, it will be necessary to deliver various cargoes to mitochondria in living cells. However, only a limited number of approaches are available for accomplishing this. In this chapter, we discuss problems associated with mitochondrial delivery systems and mitochondrial gene expression, and propose a strategy for overcoming these problems based our current efforts. To this end, we highlight a MITO-Porter, a mitochondrial delivery system, and show some examples of the regulation of mitochondrial gene expression including mitochondrial RNA knockdown and mitochondrial transgene expression.