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Updated: May 23, 2026

Isolation of Human Myoblasts, Assessment of Myogenic Differentiation, and Store-operated Calcium Entry Measurement
Published on: July 26, 2017
DDRGK1 regulates muscle development by maintaining mitochondrial calcium homeostasis and oxidative phosphorylation
Ping Li1, Lingfei Li1, Mali Guo1
1Department of Animal Genetics, Breeding and Reproduction, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210000, China.
Background:
Mitochondrial calcium homeostasis is essential for oxidative phosphorylation (OXPHOS) and cellular energy production. DDRGK1 is an ER‑localized adaptor protein, which is critical for maintaining ER homeostasis, protein stability, and organelle communication. However, the role of DDRGK1 in regulating mitochondrial function remains largely unknown. This study aims to define the role of DDRGK1 in mitochondrial calcium signaling and bioenergetics.
Methods And Results:
Through biochemical analyses in cellular models, we identify DDRGK1 as a direct interactor and stabilizer of IP3R, preventing its ubiquitin-mediated degradation. DDRGK1 deficiency reduces IP3R protein levels, impairing mitochondrial calcium uptake and OXPHOS activity, as assessed by respirometry and ATP measurements. Consequent bioenergetic deficits are accompanied by calcium overload-induced ER stress, which activates C/EBP-homologous protein (CHOP) and suppresses the PGC‑1α pathway, thereby inhibiting mitochondrial biogenesis.
Conclusions:
The DDRGK1-IP3R axis constitutes a critical regulatory module in mitochondrial calcium signaling and energy metabolism. Disruption of this axis underlies bioenergetic failure and provides mechanistic insight into the pathogenesis of skeletal muscle metabolic disorders and related mitochondrial diseases.
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