TFEB activation triggers pexophagy for functional adaptation against oxidative stress in calcium deficiency condition

Abstract

Calcium is a ubiquitous intracellular messenger which regulates expression of various genes involved in cell proliferation, differentiation and motility. At cellular level, intracellular calcium homeostasis is maintained by calcium transporters, pumps, uptakes and storage system. Deficiency of calcium level has been linked to severe clinical phenotype and life threatening arrhythmia. Number of studies suggest the involvement of calcium in diverse metabolic pathway however, effect of calcium on cellular level remains elusive. To elaborate the essentialness of calcium in cell homeostasis, we showed that calcium deficiency increases reactive oxygen species (ROS) production which further induces pexophagy, an autophagic degradation of peroxisome. Also, ROS production in calcium deficiency inactivates mTORC1, which activates transcription factor EB (TFEB). However, treatment with antioxidant, Nacetyl-l-cysteine (NAC) and autophagy inhibitor, chloroquine inhibited nuclear translocation of TFEB. Taken together, our data suggest pexophagy through ROS-mediated TFEB activation occurs due to calcium deficiency.