Abstract
Mitochondrial dysfunction either causes or at least contributes to a large number of human diseases. Malfunctioning mitochondria are associated with several adult-onset diseases and the accumulation of somatic mutations in the mitochondrial genome has been suggested to be involved in aging, age-related neurodegenerative diseases, as well as cancer. Also, an increasing number of xenobiotics and pharmaceuticals are being recognized to manifest their toxicity by interfering with mitochondrial functions. Consequently, the targeting of small drug molecules to mitochondria may provide the basis for a large variety of future cytoprotective and cytotoxic therapies: the targeting of antioxidants into the mitochondrial matrix may protect mitochondria from oxidative stress caused by a variety of insults, perhaps even contribute to slowing down the natural aging process; the mitochondria-specific targeting of naturally occurring toxins or synthetic drugs such as photosensitizers may open up avenues for new anticancer therapies. Moreover, delivering molecules known to trigger apoptosis by directly acting on mitochondria may overcome the apoptosis-resistance of many cancer cells and drugs able to target mitochondrial uncoupling proteins may become a basis for treating obesity. This review discusses current approaches for the design and delivery of small biologically active molecules to and into mitochondria of living mammalian cells and the possible therapeutic applications of such approaches.
Keywords: mitochondria, drug targeting, drug design, mitochondriotropics, mitochondrial disease
24