Authors
Seemanti Aditya, Amal Kanti Bera
Published in
Cell communication and signaling : CCS. Jun 25, 2026. Epub Jun 25, 2026.
Abstract
PIGBOS is a recently identified 54-amino acid microprotein localized to the mitochondrial outer membrane and implicated in the endoplasmic reticulum (ER) stress response. Here, we identify a previously unrecognized role for PIGBOS in cellular Ca2+ homeostasis. Manipulation of PIGBOS expression in HEK293T cells revealed that PIGBOS enhances Ca2+ signaling by promoting ER Ca2+ release through inositol 1,4,5-trisphosphate (IP3) receptors and subsequent mitochondrial Ca2+ uptake in response to histamine stimulation. In contrast, siRNA-mediated depletion or genetic ablation of PIGBOS markedly attenuated these responses. PIGBOS influenced Ca2+ transfer from the ER to mitochondria without affecting direct mitochondrial Ca2+ uptake and also promoted store-operated Ca2+ entry. Functional analyses demonstrated that the interaction of PIGBOS with the ER-resident chloride channel CLCC1 via its C-terminal region is required for this activity. Network analysis predicted a direct association between PIGBOS and CLCC1, as well as indirect connections with core Ca2+ signaling components, including IP3 receptors, STIM1, Orai1, and SERCA, whose expression was altered upon modulation of PIGBOS abundance. Loss of PIGBOS impaired mitochondrial respiration, reduced ATP production, and increased reactive oxygen species. Together, these findings establish PIGBOS as a key regulator of ER-mitochondrial Ca2+ signaling that couples Ca2+ dynamics to mitochondrial bioenergetics and cellular stress responses.
PMID:
42351194
Bibliographic data and abstract were imported from PubMed on 26 Jun 2026.
Read full publication at:
Please sign in
to see all details.
Advertisement
Stats
- Recommendations n/a n/a positive of 0 vote(s)
- Views 7
- Comments 0