Impact of tauroursodeoxycholic acid and 4-phenylbutyric acid on mitochondrial functions and morphology of SH-SY5Y cells

The aim of our work was to study impact of tauroursodeoxycholic acid (TUDCA), 4-phenylbutyric acid (PBA) and their combination on mitochondrial functions and morphology. TUDCA, PBA and their combination have a significant impact on mitochondrial respiration. Although both TUDCA and PBA are considered to be chemical chaperones influencing endoplasmic reticulum (ER) stress, they affect mitochondrial respiration in a specific way. While TUDCA decreases ROUTINE, maximal, succinate-driven maximal, ATP-coupled and leak respirations; PBA increases spare respiratory capacity (SRC). Combination of TUDCA with PBA increases ROUTINE, maximal, succinate driven maximal and ATP-coupled respirations and SRC. TUDCA, PBA and their combination exhibits positive impact on mitochondria elongation and do not induce expression of proteins involved in mitochondrial fusion and unfolded protein response. Our results do not indicate the impact of either TUDCA or PBA on ER stress since pre-treatment of the cells with either TUDCA or PBA does not significantly affect tunicamycin-induced expression of HRD1, GRP78 and SEL1L. The impact of PBA and combination of TUDCA with PBA on mitochondrial functions might be associated with their possible neuroprotective effects. Although TUDCA exhibits positive effect on inner mitochondrial membrane, the possible neuroprotective effect of TUDCA might involve mechanism distinct from modification of mitochondrial functions.