Related Experiment Video

Updated: Jan 15, 2026

Understanding the Changes in Mitochondrial Morphology through Dynamic and Three-dimensional Fluorescence Micrographs
08:15

Understanding the Changes in Mitochondrial Morphology through Dynamic and Three-dimensional Fluorescence Micrographs

Published on: August 15, 2025

995

PGAM5 cleavage and oligomerization equilibrates mitochondrial dynamics under stress by regulating DRP1 function

Sudeshna Nag1, Kaitlin Szederkenyi1,2, Christopher M Yip1,2

  • 1Department of Biochemistry, University of Toronto, MaRS Centre West Tower, 661 University Ave., M5G 1M1, Toronto, Canada.

Journal of Cell Science
|October 9, 2025
PubMed

Insights

Phosphoglycerate mutase 5 (PGAM5) protein activity is regulated by its oligomerization and cleavage. These events control PGAM5

Area of Science:

  • Mitochondrial biology and cellular dynamics.
  • Protein regulation and post-translational modifications.

Background:

  • Mitochondrial dynamics are governed by dynamin GTPases like mitofusin 1 (MFN1), mitofusin 2 (MFN2), and dynamin-related protein 1 (DRP1).
  • Phosphoglycerate mutase 5 (PGAM5) influences MFN2 and DRP1 phosphorylation and function, but its regulatory mechanisms remain unclear.

Purpose of the Study:

  • To elucidate the precise regulation of phosphoglycerate mutase 5 (PGAM5) activity.
  • To investigate the role of PGAM5 oligomerization and localization in controlling mitochondrial dynamics.

Main Methods:

  • Analysis of PGAM5 oligomerization states (dodecamer vs. dimer) under cellular stress conditions.
  • Assessment of PGAM5's differential binding affinity to MFN2 and DRP1.
  • Investigation of PGAM5 cleavage by inner mitochondrial proteases PARL and OMA1.
  • Tracking of PGAM5 relocalization to the cytosol post-cleavage.

Main Results:

  • Under depolarization and metabolic stress, PGAM5 shifts from dodecamers to dimers.
  • PGAM5 dimers exhibit altered affinities for MFN2 and DRP1 compared to dodecamers.
  • PGAM5 undergoes cleavage by PARL and OMA1, with a portion translocating to the cytosol.

Conclusions:

  • PGAM5 oligomerization state (dodecamer vs. dimer) is a key regulator of its function.
  • Cleavage-induced relocalization of PGAM5 to the cytosol further modulates its activity.
  • These regulatory events are critical for controlling mitochondrial dynamics during cellular stress.
Keywords:
DRP1Glucose starvationMFN2Mitochondrial morphologyPGAM5

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