Modulation of cell fate by tauroursodeoxycholic acid: All paths lead to mitochondria

Abstract

Specific endogenous bile acids, such as ursodeoxycholic (UDCA) acid and its taurine conjugated form, tauroursodeoxycholic acid (TUDCA), are potent modulators of cell fate by regulating pathways that involve mitochondria. Curiously, emerging evidence suggests that mitochondrial changes induced by TUDCA result from its influence on mitochondrial redox state, mitochondrial membrane permeabilization, mitochondrial apoptosis and mitophagy. In fact, the pleiotropic cellular function of TUDCA ranges from its direct interaction with mitochondrial membranes to modulation of kinase survival pathways or gene expression that ultimately impact on mitochondria. Further, regulation of the functional endoplasmatic reticulum (ER)-mitochondria unit by this bile acid has also been proven as a key counterpart of mitochondria-targeted TUDCA effect. In this chapter, we summarize mechanisms by which this hydrophilic bile acid affects mitochondria and subsequently cell survival, cell cycle and differentiation. We also discuss the potential therapeutic application of TUDCA in several pathological conditions associated with mitochondrial dysfunction.