Premium
Serendipity and the Discovery of Novel Compounds That Restore Mitochondrial Plasticity
Author(s) -
Szeto H H,
Birk A V
Publication year - 2014
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.2014.174
Subject(s) - bioenergetics , mitochondrion , adenosine triphosphate , serendipity , drug discovery , cardiolipin , biology , microbiology and biotechnology , organism , computational biology , chemistry , biochemistry , genetics , membrane , philosophy , epistemology , phospholipid
The mitochondrial electron transport chain (ETC) plays a central role in energy generation in the cell. Mitochondrial dysfunctions diminish adenosine triphosphate (ATP) production and result in insufficient energy to maintain cell function. As energy output declines, the most energetic tissues are preferentially affected. To satisfy cellular energy demands, the mitochondrial ETC needs to be able to elevate its capacity to produce ATP at times of increased metabolic demand or decreased fuel supply. This mitochondrial plasticity is reduced in many age‐associated diseases. In this review, we describe the serendipitous discovery of a novel class of compounds that selectively target cardiolipin on the inner mitochondrial membrane to optimize efficiency of the ETC and thereby restore cellular bioenergetics in aging and diverse disease models, without any effect on the normal healthy organism. The first of these compounds, SS‐31, is currently in multiple clinical trials. Clinical Pharmacology & Therapeutics (2014); 96 6, 672–683. doi: 10.1038/clpt.2014.174