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Updated: Mar 31, 2026

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Microvillus inclusion disease-associated MYO5B deficiency impairs endosome-to-mitochondrion iron transfer

Chang Sun1, Changsen Leng1,2, Mingyue Sun1

  • 1Department of Biomedical Sciences, University of Groningen, University Medical Center Groningen, 9713AV Groningen, The Netherlands.

Gastroenterology Report
|March 30, 2026
PubMed
Abstract

Insights

MYO5B deficiency causes microvillus inclusion disease (MVID) by impairing iron transfer to mitochondria, leading to cellular dysfunction. Restoring mitochondrial function presents a potential therapeutic strategy for MVID patients.

Area of Science:

  • Cell Biology
  • Genetics
  • Mitochondrial Biology

Background:

  • Microvillus inclusion disease (MVID) results from MYO5B deficiency, causing nutrient malabsorption and diarrhea.
  • Metabolic abnormalities in MVID intestinal tissue are observed, but the link to MYO5B and the mechanism remain unclear.

Purpose of the Study:

  • To investigate the impact of MYO5B deficiency on mitochondria, key regulators of cellular metabolism.
  • To elucidate the underlying mechanisms of mitochondrial dysfunction in MYO5B deficiency.

Main Methods:

  • Examined intestinal tissue from MVID patients and intestine-specific myo5b-knockout mice.
  • Utilized CRISPR-Cas9 to create MYO5B knockout Caco2 cells and site-directed mutagenesis for MYO5B variants.
  • Assessed mitochondrial function using fluorescence indicators, protein analysis, and high-resolution respirometry.

Main Results:

  • MYO5B deficiency led to mitochondrial fragmentation, impaired respiration, reduced membrane potential, and increased oxidative stress in Caco2 cells.
  • Restoration of MYO5B function normalized mitochondrial membrane potential, while MVID-associated mutants did not.
  • Reduced association between mitochondria and transferrin-loaded endosomes, decreased mitochondrial iron content, and endosomal iron accumulation were observed in MYO5B-deficient cells.

Conclusions:

  • MYO5B deficiency disrupts endosome-to-mitochondrial iron transfer, causing mitochondrial dysfunction.
  • These findings suggest targeting mitochondrial function as a therapeutic approach for MVID.
Keywords:
MYO5Bintestinemicrovillus inclusion diseasemitochondria

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