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Updated: Feb 26, 2026

Sensitive Measurement of Mitophagy by Flow Cytometry Using the pH-dependent Fluorescent Reporter mt-Keima
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Mitofusin MFN2 acts as a molecular sensor preventing protein aggregation and mitophagy, with a protective effect

Mariana Joaquim1, Maike F Dohrn2, Arnaud Chevrollier3

  • 1Institute for Genetics, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD) and Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.

Autophagy Reports
|February 25, 2026
PubMed

Insights

Mitofusin 2 (MFN2) is vital for mitochondrial health, beyond its role in fusion. MFN2 also maintains cellular protein quality control, a function impaired in Charcot-Marie-Tooth disease.

Area of Science:

  • Cell Biology
  • Mitochondrial Dynamics
  • Neurogenetics

Background:

  • Mitochondria are essential for cellular energy and function, undergoing dynamic remodeling.
  • Mitofusin 2 (MFN2) is a key protein regulating mitochondrial fusion and inter-organelle communication.
  • MFN2 dysfunction is implicated in Charcot-Marie-Tooth type 2A (CMT2A) and metabolic disorders.

Purpose of the Study:

  • To elucidate the fusion-independent functions of MFN2.
  • To investigate MFN2's role in maintaining proteostasis and mitophagy.
  • To understand how MFN2 variants associated with CMT2A affect these functions.

Main Methods:

  • Biochemical assays to study MFN2 interactions.
  • Cellular models of MFN2 dysfunction.
  • Analysis of proteostasis and mitophagy pathways.

Main Results:

  • MFN2 binds the chaperone HSPA8/HSC70 and the proteasome.
  • This interaction is crucial for mitochondrial and cellular protein quality control.
  • CMT2A-associated MFN2 variants disrupt this proteostasis function.

Conclusions:

  • MFN2 plays a critical role in proteostasis and mitophagy independently of its fusion activity.
  • Impaired proteostasis due to MFN2 dysfunction contributes to CMT2A pathogenesis.
  • Targeting MFN2-mediated protein quality control may offer therapeutic avenues for CMT2A and related diseases.
Keywords:
Charcot–Marie–Tooth type 2A (CMT2A)HSPA8/HSC70MFN2; protein import; proteasome; VCP/p97PINK1apoptosismitophagyproteostasis

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