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PIGBOS-CLCC1 interaction shapes cellular calcium dynamics and energy metabolism
Seemanti Aditya1, Amal Kanti Bera2
1Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai, Tamil Nadu, 600036, India.
Cell Communication and Signaling : CCS
|June 26, 2026
Summary
PIGBOS, a microprotein, regulates cellular calcium (Ca2+) signaling by enhancing endoplasmic reticulum (ER) Ca2+ release and mitochondrial Ca2+ uptake. Its loss impairs mitochondrial function and increases cellular stress.
Area of Science:
- Cell Biology
- Mitochondrial Biology
- Calcium Signaling
Background:
- PIGBOS is a microprotein involved in endoplasmic reticulum (ER) stress response.
- Its role in cellular calcium (Ca2+) homeostasis was previously unrecognized.
Purpose of the Study:
- To investigate the novel function of PIGBOS in cellular Ca2+ homeostasis.
- To elucidate the mechanisms by which PIGBOS regulates Ca2+ signaling and mitochondrial function.
Main Methods:
- Manipulation of PIGBOS expression in HEK293T cells.
- siRNA-mediated depletion and genetic ablation of PIGBOS.
- Analysis of Ca2+ signaling via inositol 1,4,5-trisphosphate (IP3) receptors and store-operated Ca2+ entry.
- Investigation of PIGBOS interaction with CLCC1.
- Network analysis of Ca2+ signaling components.
- Assessment of mitochondrial respiration, ATP production, and reactive oxygen species (ROS).
Main Results:
- PIGBOS enhances ER Ca2+ release and mitochondrial Ca2+ uptake, promoting Ca2+ signaling.
- PIGBOS interacts with CLCC1, which is crucial for its Ca2+ regulatory activity.
- Loss of PIGBOS impairs mitochondrial respiration, reduces ATP production, and increases ROS.
- PIGBOS modulates the expression of key Ca2+ signaling proteins (IP3 receptors, STIM1, Orai1, SERCA).
Conclusions:
- PIGBOS is a key regulator of ER-mitochondrial Ca2+ signaling.
- PIGBOS couples Ca2+ dynamics to mitochondrial bioenergetics.
- PIGBOS plays a significant role in cellular stress responses through its regulation of Ca2+ homeostasis.
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