MICU1's calcium sensing beyond mitochondrial calcium uptake

The discovery of MICU1 as gatekeeper of mitochondrial calcium (_mCa²⁺) entry has transformed our understanding of _mCa²⁺ flux. Recent studies revealed an additional role of MICU1 as a Ca²⁺ sensor at MICOS (mitochondrial contact site and cristae organizing system). MICU1's presence at MICOS suggests its involvement in coordinating Ca²⁺ signaling and mitochondrial ultrastructure. Besides its role in Ca²⁺ regulation, MICU1 influences cellular signaling pathways including transcription, epigenetic regulation, metabolism, and cell death, thereby affecting human health. Here, we summarize recent findings on MICU1's canonical and noncanonical functions, and its relevance to human health and diseases.