Mitophagy and Disease: New Avenues for Pharmacological Intervention

Robert      Taylor; Scott      J. Goldman

Abstract

The process of intracellular macromolecular degradation known as macroautophagy has long been associated with the degradation of mitochondria. Recent studies have provided evidence that the process of mitochondria degradation via autophagy, now referred to as mitophagy, appears to be specifically targeted to mitochondria and highly regulated under both physiologic and pathologic conditions. This article provides a review of key developments in mitophagy research, including background information on the history, mechanisms, and regulation of macroautophagy, as well as discoveries that have enhanced our understanding of the specificity and independent regulation of mitophagy. This is followed by an analysis of how our current understanding of the mechanics and regulation of mitophagy may be exploited to yield pharmacological interventions for mitochondria-associated diseases. As yet, the potential for mitophagy- related pharmacological treatments for disease remains largely untapped. However, rapid progress in our understanding of both mitophagy and the pathology of mitochondria-related diseases is leading us towards the convergence of science and medicine which will inevitably result in new and potent pharmacological therapies for the treatment of these maladies.

Keywords: Mitophagy, autophagy, PINK1, Parkin, MMP, MPT, chloroquine, Sacchromyces cerevisiae, Macroautophagy, eubacteria