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The endoplasmic reticulum protein FAM134B acts as a regulator of mitochondrial morphology

Sebabrata Maity1,2, Anwesha Dutta Gupta1,2, Izaz Monir Kamal3,4

  • 1Biophysics & Structural Genomics Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata 700064, WB, India.

Journal of Cell Science
|November 3, 2025
PubMed

Insights

The endoplasmic reticulum protein FAM134B interacts with DRP1 to regulate mitochondrial fission. Reduced FAM134B causes mitochondrial hyperfusion and is linked to aging and Parkinson's disease.

Area of Science:

  • Cell Biology
  • Mitochondrial Dynamics
  • Autophagy

Background:

  • Endoplasmic reticulum (ER) and mitochondria interactions are crucial for cellular functions.
  • FAM134B (RETREG1) regulates ER shape and ER-mitochondria dual autophagy.
  • FAM134B's role in mitochondrial dynamics was previously unknown.

Purpose of the Study:

  • To investigate the direct involvement of FAM134B in mitochondrial dynamics.
  • To identify the molecular mechanisms linking FAM134B to mitochondrial morphology.
  • To explore the relevance of FAM134B in aging and neurodegenerative diseases.

Main Methods:

  • Co-immunoprecipitation to assess protein interactions.
  • Cellular assays to analyze mitochondrial morphology and DRP1 recruitment.
  • Analysis of FAM134B levels in aging and Parkinson's disease models.

Main Results:

  • FAM134B directly interacts with DRP1, a key protein in mitochondrial fission.
  • FAM134B depletion results in mitochondrial hyperfusion due to impaired DRP1 recruitment.
  • Decreased FAM134B levels correlate with aging and Parkinson's disease pathology.

Conclusions:

  • FAM134B acts as an ER-associated factor that governs mitochondrial morphology and dynamics.
  • The FAM134B-DRP1 interaction is critical for maintaining mitochondrial fission.
  • FAM134B dysfunction may contribute to age-related mitochondrial changes and Parkinson's disease.
Keywords:
DRP1FAM134BFissionMitochondrial hyperfusion

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