| 2012 |
MCUR1 (CCDC90A) is an integral inner mitochondrial membrane protein that physically binds to MCU and is required for ruthenium-red-sensitive, MCU-dependent mitochondrial Ca2+ uptake. MCUR1 knockdown abrogates Ca2+ uptake by energized mitochondria in intact and permeabilized cells without altering MCU localization. Loss of MCUR1 disrupts oxidative phosphorylation, lowers cellular ATP, and activates AMPK-dependent pro-survival autophagy. |
Co-immunoprecipitation (MCU-MCUR1 binding), siRNA knockdown with Ca2+ uptake assays in intact and permeabilized cells, ruthenium red sensitivity assays, ATP measurements, AMPK activation assays |
Nature cell biology |
High |
23178883
|
| 2015 |
Suppression of CCDC90A (MCUR1) in human fibroblasts produces a specific cytochrome c oxidase (COX) assembly defect, resulting in decreased mitochondrial membrane potential and reduced mitochondrial Ca2+ uptake capacity. The yeast homolog Fmp32 deletion also causes COX deficiency, indicating the function is evolutionarily conserved. This study argues CCDC90A acts indirectly on Ca2+ uptake via membrane potential, not as a direct MCU regulator. |
siRNA knockdown in human fibroblasts, COX assembly assays, mitochondrial membrane potential measurements, Ca2+ uptake capacity assays, genetic deletion of yeast homolog fmp32, rescue with wild-type cDNA in COX-deficient patient fibroblasts |
Cell metabolism |
High |
25565209
|
| 2016 |
MCUR1 functions as a scaffold factor for the MCU complex, binding both MCU and EMRE. Loss of MCUR1 in mouse cardiomyocytes and endothelial cells severely impairs mitochondrial Ca2+ uptake current (IMCU). The minimal coiled-coil domains of both MCU and MCUR1 are necessary for heterooligomeric complex formation. Loss of MCUR1 perturbs MCU complex assembly and impairs mitochondrial bioenergetics, cell proliferation, and migration while eliciting autophagy. |
Protein binding analyses identifying coiled-coil interaction domains, IMCU current measurements (electrophysiology), Co-IP of MCUR1 with MCU and EMRE, conditional genetic deletion in cardiomyocytes and endothelial cells, cell proliferation and migration assays |
Cell reports |
High |
27184846
|
| 2016 |
MCUR1 expression regulates the Ca2+ threshold required for mitochondrial permeability transition (mPT). Expression of MCUR1 in Drosophila cells conferred mPT sensitivity to electrophoretic Ca2+ uptake; inhibiting MCUR1 in mammalian cells increased the Ca2+ threshold required to induce mPT. This resistance to Ca2+ overload improved cell survival. The effect was specific to Ca2+-induced permeability transition. |
Cross-species complementation (MCUR1 expression in Drosophila cells), MCUR1 knockdown in mammalian cells, mitochondrial permeability transition assays with Ca2+ titration, cell survival assays |
Proceedings of the National Academy of Sciences of the United States of America |
High |
26976564
|
| 2019 |
The head domain of MCUR1 directly interacts with the mitochondrial calcium uniporter (MCU) and is destabilized upon Ca2+ binding. Crystal structures of the related CCDC90B head domain and archaeal Kcr-0859 reveal a conserved head-neck-stalk-anchor architecture with a β-layer neck. MCUR1 and CCDC90B are part of a heterogeneous group of trimeric membrane-anchored coiled-coil proteins conserved from prokaryotes to eukaryotic organelles. |
Crystal structure determination of CCDC90B head domain and archaeal Kcr-0859, domain deletion/mutagenesis studies of MCUR1, Ca2+ binding and destabilization assays, sequence analysis defining domain architecture |
Structure (London, England : 1993) |
High |
30612859
|
| 2019 |
MCUR1-mediated mitochondrial Ca2+ uptake activates the ROS/Nrf2/Notch1 pathway, which drives EMT via Snail in hepatocellular carcinoma cells. MCUR1 promotes in vitro invasion and in vivo metastasis. Inhibition of ROS, mitochondrial Ca2+ uptake, Nrf2, or Notch1 suppresses MCUR1-induced EMT. Mitochondrial Ca2+-buffering with parvalbumin inhibits the pathway and MCUR1-induced EMT and metastasis. |
MCUR1 knockdown/overexpression in HCC cells, immunofluorescent staining for EMT markers, in vitro invasion assays, in vivo metastasis assays, ROS measurement, pathway inhibition with chemical inhibitors and parvalbumin treatment, Western blot |
Journal of experimental & clinical cancer research : CR |
Medium |
30909929
|
| 2017 |
MCUR1-mediated mitochondrial Ca2+ uptake elevates mitochondrial ROS production, which drives AKT/MDM2-mediated P53 degradation to inhibit intrinsic apoptosis and promote HCC cell survival and proliferation. MCUR1 overexpression enhances MCU-dependent Ca2+ uptake; knockdown impairs it. Mitochondrial Ca2+ buffering with parvalbumin inhibits HCC cell growth. |
MCUR1 knockdown/overexpression in HCC cells, mitochondrial Ca2+ uptake measurements, ROS measurement, P53 degradation assays, AKT/MDM2 pathway analysis, in vivo xenograft assays (TUNEL, Ki67 staining), parvalbumin treatment |
Antioxidants & redox signaling |
Medium |
28938844
|
| 2020 |
Yeast homologs of MCUR1, Put6 and Put7, form a large hetero-oligomeric complex tethered to the inner mitochondrial membrane and regulate mitochondrial proline metabolism. Loss of this complex perturbs mitochondrial proline homeostasis and cellular redox balance; cells lacking Put6 or Put7 cannot utilize proline. This defect is rescued by heterologous expression of human MCUR1, demonstrating functional conservation of MCUR1 homologs in mitochondrial metabolic scaffolding beyond Ca2+ regulation. |
Genetic deletion of Put6/Put7 in S. cerevisiae, mitochondrial fractionation, hetero-oligomeric complex characterization, proline utilization assays, metabolomics, redox assays, heterologous complementation with human MCUR1 |
Nature communications |
High |
32978391
|
| 2025 |
MCUR1 knockdown reduces mitochondrial Ca2+ uptake and concomitantly increases cytosolic Ca2+, which reduces erythropoiesis via the CAMKK2-AMPK-mTOR signaling axis under both hypoxia and normoxia. A functional SNP (rs61644582) acts as an expression QTL reducing MCUR1 transcription, and attenuates erythropoiesis in Tibetan highlanders. |
MCUR1 knockdown with single-cell RNA sequencing, mitochondrial Ca2+ uptake measurements, cytosolic Ca2+ measurements, pharmacological inhibition of CAMKK2-AMPK-mTOR pathway components, erythropoiesis differentiation assays, whole-genome sequencing and eQTL analysis |
Cell genomics |
Medium |
40043709
|
| 2026 |
A homozygous MCUR1 nonsense mutation in a human patient causes compromised mitochondrial Ca2+ uptake (stimulated by histamine or rising extracellular Ca2+), increased autophagic flux (LAMP2, LC3B markers), and autophagic vacuolar myopathy. Critically, MCUR1 loss-of-function does NOT alter MCU complex assembly, MCU subcellular localization, or resting mitochondrial membrane potential, indicating MCUR1 promotes MCU activity without being required for MCU complex assembly or stability. |
Patient fibroblasts and muscle biopsy analysis, mitochondrial Ca2+ uptake assays, autophagy flux assays, Western blot for MCU complex components, histological analysis, mitochondrial membrane potential measurement |
Acta neuropathologica communications |
Medium |
42087238
|
| 2025 |
MCUR1 and its paralog CCDC90B form a hetero-oligomeric complex whose stability depends on MCUR1. Loss of MCUR1 exerts a dominant-negative effect on CCDC90B. Deletion of MCUR1/CCDC90B homologs in S. pombe (which lacks MCU) impairs lipid and amino acid metabolism; this is rescued by human MCUR1 expression, indicating a Ca2+-independent scaffold function. MCUR1 deficiency in patient fibroblasts upregulates autophagy, perturbs non-essential amino acid metabolism, and limits biosynthetic capacity. |
Complex stability assays (co-IP, protein abundance measurement), S. pombe genetic deletion with metabolic rescue by human MCUR1 expression, patient serum metabolomics, patient fibroblast functional assays (autophagy, amino acid metabolism, proliferation, migration) |
bioRxivpreprint |
Medium |
bio_10.1101_2025.10.14.682030
|