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Updated: Sep 30, 2026
Analyzing the Functions of Mast Cells In Vivo Using 'Mast Cell Knock-in' Mice
Published on: May 27, 2015
MITF-associated metabolic signature in mast cells: A potential link to food anaphylaxis
Laia Ollé1, Mónica Barrios2, Lihong Song1
1Biochemistry and Molecular Biology Unit, Biomedicine Department. Faculty of Medicine, University of Barcelona. Barcelona, Spain; Multidisciplinary and translational research in inflammation and immunoallergy (METRI(2) A), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
Background:
Microphthalmia-associated transcription factor (MITF) is a master regulator of mast cell (MC) differentiation and effector function and is essential for anaphylaxis (severe allergic reactions). Although MITF has been linked to mitochondrial regulation through pyruvate dehydrogenase, whether it broadly controls mitochondrial fitness and metabolic programs that exacerbate MC activation remains unclear.
Objective:
To determine how MITF regulates MC mitochondrial function and metabolic fitness beyond pyruvate dehydrogenase control, and to define its contribution to heightened MC activation and food anaphylaxis.
Methods:
MITF was silenced, pharmacologically inhibited, or overexpressed in human MCs, followed by IgE- and MRGPRX2-dependent activation. Transcriptomic profiling, and mitochondrial functional analyses were then performed. In parallel, MCs from patients with food anaphylaxis and from healthy controls were analyzed to assess clinical relevance.
Results:
Transcriptomic analysis of MITF-silenced MCs revealed a distinct metabolic signature characterized by downregulation of mitochondrial pathways and metabolic cellular compartments. MITF knockdown reduced mitochondrial fission, membrane potential, mitochondrial respiration, and mitochondrial marker expression of TOM20 and COX-IV, supporting a role for MITF in mitochondrial activity and metabolic regulation. Furthermore, MCs from patients with food anaphylaxis exhibited increased MITF expression, elevated mitochondrial markers, enhanced mitochondrial respiration, and a glycolytic shift after allergen activation, compared with those from sensitized and healthy individuals. Notably, pharmacological inhibition of MITF reduced mitochondrial membrane potential in patient-derived MCs.
Conclusions:
MITF is a central regulator of MC mitochondrial function and is associated with enhanced metabolic activity in anaphylaxis, highlighting MITF-driven pathways as potential therapeutic targets in MC-mediated allergic disease.
