Fig. 7: Working model. | Nature Communications

Fig. 7: Working model.

From: GPAT4 sustains endoplasmic reticulum homeostasis in endocardial cells and safeguards heart development

Fig. 7

(NORMAL) Under the normal condition, GPAT4 in the endocardial cells binding with EIF2S1/EIF2α to sustain ER homeostasis and fine-tunes ER-Mito communications to safeguard endocardial development. (GPAT4 LOSS) In the absence of GPAT4, ER homeostasis is disrupted and ER stress response is triggered by phosphorylating EIF2S1/EIF2α, leading to enhanced ER-Mito communications, which in turn, causes Mito Ca2+ overloading and mtDNA escape. As a result, cGAS-STING-type I interferon response is elicited, which induces endocardial apoptosis. In the end, this leads to defective trabecular compaction (poor myocardial development) and excessive trabeculation. (Created in BioRender. zhao, t. (2025) https://BioRender.com/m79n092).

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