Mitochondrial microprotein PIGBOS1 is possibly associated with cellular calcium homeostasis and neuro-protection

Abstract

Background: Calcium ion (Ca2+) plays a vital role in many physiological processes like memory formation, cell-cell communication,
secretion, neurotransmission, cell survival, and death. The concerted activities of several transporters and ion channels maintain an
optimum concentration of Ca2+ inside the cell. Disruption of calcium homeostasis may cause abnormal protein aggregation, leading to
several neurodegenerative diseases like Alzheimer’s disease and Parkinson’s disease (PD). Objective: Several pieces of evidence indicate
that altered calcium homeostasis, oxidative stress, and endoplasmic reticulum (ER) stress are intimately related to the development of PD.
PIGBOS1, a recently discovered mitochondrial microprotein, has been shown to play an essential role in ER stress response through its
interaction with an ER-resident chloride channel CLCC1. Materials and Methods: In the present study, we investigated the role of PIGBOS1
in cellular calcium homeostasis by monitoring Ca2+ dynamics in the ER, cytoplasm, and mitochondria using genetically encoded Ca2+
indicators. Results: In the resting state, PIGBOS1-overexpressed HEK-293T cells exhibited a higher level of basal Ca2+ in the ER. Further,
cytosolic and mitochondrial Ca2+ rise following ionomycin/ histamine treatment was higher in PIGBOS1-overexpressed cells. Conclusion:
Taken together, it implies that PIGBOS1 is an integral part of the cellular Ca2+ signaling network. We have discussed the possible role of
PIGBOS1 in neurodegenerative diseases like PD.