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Updated: Oct 13, 2026

A Thermoplasmonic Approach for Investigating Plasma Membrane Repair in Living Cells and Model Membranes
Published on: January 19, 2024
ATAD-3 couples plasma membrane injury to mitochondrial Ca2+ signaling
Shiqi Xu1,2, Yi Peng1, Hengda Zhou2
1Center for Stem Cell and Regenerative Medicine and Department of Burn and Wound Repair of the Second Affiliated Hospital, Zhejiang University-University of Edinburgh Institute, Zhejiang University School of Medicine, Hangzhou, 310058, China.
Abstract:
Mitochondrial Ca2+ uptake couples cellular Ca2+ signals to mitochondrial metabolism and stress responses and is primarily mediated by the mitochondrial Ca2+ uniporter (MCU). Here, we identify an ATAD-3-dependent mechanism that promotes mitochondrial Ca2+ uptake following plasma membrane injury in C. elegans. Living imaging reveals robust, albeit delayed, mitochondrial Ca2+ influx following injury in mcu-1 mutants, indicating the existence of a compensatory Ca2+ uptake mechanism. RNAi screen identifies the conserved AAA+ ATPase ATAD-3 as an essential regulator of this pathway, whereas MICU-3 acts as a negative regulator. Wounding induces ATAD-3 oligomerization and mitochondrial enrichment, which are enhanced in mcu-1 mutants. Disrupting ATAD-3 oligomerization or expression of disease-associated ATAD-3 variants abolishes wounding-induced mitochondrial Ca2+ uptake. Structure modeling predicts that oligomeric ATAD-3 adopts a channel-like architecture. These findings uncover ATAD-3 as a context-dependent regulator of mitochondrial Ca2+ homeostasis during cellular stress and provide insight into how this process may be disrupted in disease.
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