Mitochondrial function is critical for neuronal activity and systemic metabolic adaptation. In this issue, Li et al. (https://doi.org/10.1083/jcb.202408050) identify TMBIM-2 as a key regulator of calcium dynamics, coordinating the neuronal-to-intestinal mitochondrial unfolded protein response (UPRmt), pathogen-induced aversive learning, and aging.
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