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The Critical Role Played by Mitochondrial MITF Serine 73 Phosphorylation in Immunologically Activated Mast Cells

Lakshmi Bhargavi Paruchuru1, Sharmila Govindaraj1, Ehud Razin1

  • 1Department of Biochemistry and Molecular Biology, Institute for Medical Research Israel-Canada, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 91120, Israel.

Cells
|February 15, 2022
PubMed

Insights

Mitochondrial microphthalmia-associated transcription factor (MITF) phosphorylation at Serine 73 is crucial for mast cell activation. This finding reveals a new target for modulating immune responses in mast cells.

Area of Science:

  • Immunology
  • Cell Biology
  • Mitochondrial Biology

Background:

  • Mitochondria play a key role in mast cell immune activation.
  • Previous studies linked pyruvate dehydrogenase (PDH) inhibition to reduced mast cell degranulation and cytokine secretion.

Purpose of the Study:

  • To investigate the role of mitochondrial microphthalmia-associated transcription factor (MITF) in mast cell exocytosis.
  • To explore the link between MITF phosphorylation and mast cell activation.

Main Methods:

  • Utilized rat basophil leukemia (RBL) cells and mouse bone marrow-derived mast cells (BMMCs).
  • Examined the effects of ERK1/2 inhibition (U0126) on mast cell degranulation, cytokine secretion, and oxidative phosphorylation (OXPHOS).
  • Investigated the impact of MITF Serine 73 phosphorylation and its mimicking mutant (MITF-S73D) on mitochondrial activity.

Main Results:

  • Mast cell degranulation, cytokine secretion, and OXPHOS correlate with mitochondrial MITF Serine 73 phosphorylation.
  • ERK1/2 inhibition led to MITF Serine 73 dephosphorylation, reduced OXPHOS, and decreased mast cell reactivity.
  • A phosphorylation-mimicking MITF-S73D mutant enhanced mitochondrial activity and supported mast cell degranulation.

Conclusions:

  • Mitochondrial MITF Serine 73 phosphorylation is a key regulator of mast cell immunological activation.
  • This phosphorylation event influences mast cell degranulation, cytokine secretion, and oxidative phosphorylation.
  • Targeting MITF Serine 73 phosphorylation offers a potential strategy for modulating mast cell-mediated immune responses.
Keywords:
allergycytokinesdegranulationextracellular signal-regulated kinasemast cellsmicrophthalmia-associated transcription factormitochondriapyruvate dehydrogenase

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