SCHEME 1.

Role of the mitochondrial uniporter regulator MICU1 in calcium buffering and ER stress. ⁺AuNPs can be used to examine the role of MICU1. ⁺AuNPs cause plasma membrane depolarization, allowing Ca²⁺ influx, which is normally buffered by mitochondria regulated by MICU1, which also has an antiapoptotic role. Separately, MICU1 may normally prevent ER stress such as that induced by ⁺AuNPs. Thus, we propose that enhanced MICU1 expression or activity is a key mechanism that prevents the desired cytotoxic effects of nanoparticles and other agents in conditions such as cancer.