Involvement of Mitochondrial Dysfunction on the Toxic Effects Caused by Drugs of Abuse and Addiction

This chapter highlights the evidences supporting the involvement of mitochondrial dysfunction on the toxic effects caused by drug abuse and addiction. The tricarboxylic acid (TCA) cycle is a central part of the energetic metabolism that contributes to the generation of adenosine triphosphate (ATP) by the chemical breakdown of carbohydrates, fats, and proteins. It consists of a series of chemical reactions, catalyzed by enzymes occurring inside mitochondria, called the mitochondrial matrix. Mitochondria provide cellular energy by converting oxygen and nutrients into ATP via oxidative phosphorylation, which occurs at the Electron Transport Chain (ETC), localized in the inner mitochondrial membrane. The mitochondrial biogenesis, the beginning of mitochondria "life cycle", encompasses the coordinated synthesis of nuclear DNA- and mtDNA-encoded proteins, together with membrane synthesis and the proper targeting and folding of ETC subunits. Mitochondrial fission is mediated by dynamin-related protein 1 (Drp1), a member of the dynamin family of guanosine 5'-triphosphatases (GTPases).