{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nEFhd1 is a mitochondrial Ca2⁺‐binding protein that plays a pivotal role in regulating cellular metabolism during early B‐cell development. In pro B cells, EFhd1 is highly expressed and helps maintain a balance between oxidative phosphorylation and glycolysis, thereby influencing the energy profile necessary for cell proliferation. Upon pre–B‐cell receptor expression, its downregulation facilitates a switch in metabolic activity that is critical for the timely progression from the pro to the pre B cell stage. Disruption of EFhd1 levels—whether by knockdown or prolonged expression—leads to altered mitochondrial function and an intrinsic developmental disadvantage in the B‐cell lineage."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}, {"type": "p", "children": [{"type": "t", "text": "\nIn the nervous system, EFhd1 similarly contributes to energy homeostasis and mitochondrial integrity, ensuring sufficient ATP production during the high metabolic demands of axonal growth and branching. Sensory neurons deficient in key upstream regulators of energy balance exhibit a marked reduction in EFhd1 expression, which correlates with mitochondrial dysfunction, a decrease in axonal ATP levels, and an accumulation of autophagic flux via the AMPK–Ulk pathway. The loss of EFhd1 in these neurons not only compromises mitochondrial morphology at axonal growth cones but also impairs overall axonal morphogenesis and increases neuronal apoptosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}, {"type": "p", "children": [{"type": "t", "text": "\nOverall, EFhd1 emerges as an essential modulator of mitochondrial function in diverse cellular contexts. In both developing B cells and sensory neurons, it governs critical aspects of energy metabolism and mitochondrial dynamics, ensuring proper cell differentiation and survival. The protein’s regulation of Ca2⁺‐mediated mitochondrial responses underscores its broader significance in coordinating cellular metabolism with developmental cues and stress responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}]}]}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Merle Stein, Sebastian Dütting, Dimitrios Mougiakakos, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A defined metabolic state in pre B cells governs B-cell development and is counterbalanced by Swiprosin-2/EFhd1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Differ (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/cdd.2017.52"}], "href": "https://doi.org/10.1038/cdd.2017.52"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28524857"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28524857"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Valeria Ulisse, Swagata Dey, Deborah E Rothbard, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of axonal morphogenesis by the mitochondrial protein Efhd1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Life Sci Alliance (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.26508/lsa.202000753"}], "href": "https://doi.org/10.26508/lsa.202000753"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32414840"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32414840"}]}]}]}