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Phospholipid association is essential for dynamin-related protein Mgm1 to function in mitochondrial membrane fusion

Jarungjit Rujiviphat1, Gabriela Meglei, John L Rubinstein

  • 1Department of Biochemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada.

The Journal of Biological Chemistry
|August 26, 2009
PubMed

Insights

Mgm1 (mitochondrial protein) binds to inner mitochondrial membrane lipids, enhancing its GTPase activity and promoting membrane fusion. This reveals a lipid-binding domain crucial for mitochondrial dynamics.

Area of Science:

  • Mitochondrial biology
  • Membrane biophysics
  • Protein biochemistry

Background:

  • Mgm1 is essential for mitochondrial fusion and dynamics in yeast, analogous to OPA1 in mammals.
  • The short isoform of Mgm1 (s-Mgm1) exhibits GTPase activity, self-assembly, and interaction with negatively charged phospholipids.

Purpose of the Study:

  • To investigate the interaction of s-Mgm1 with mitochondrial inner membrane lipids.
  • To elucidate the functional and structural consequences of s-Mgm1 lipid binding.
  • To understand the mechanism by which Mgm1 mediates mitochondrial inner membrane fusion.

Main Methods:

  • Lipid binding assays using phospholipids characteristic of the mitochondrial inner membrane.
  • GTPase activity assays to measure enzyme kinetics.
  • In vivo studies using s-Mgm1 mutants.
  • Electron microscopy and negative staining for structural analysis.
  • Lipid turbidity assays to assess liposome interaction.

Main Results:

  • s-Mgm1 binds to mitochondrial inner membrane lipid mixtures.
  • Lipid binding stimulates s-Mgm1 GTPase activity by approximately 50-fold.
  • Mutants defective in lipid binding or oligomerization are non-functional in vivo.
  • s-Mgm1 promotes liposome interaction and forms oligomeric rings on liposomes.
  • Structural analysis reveals Mgm1 oligomers consistent with two stacked trimers.

Conclusions:

  • A lipid-binding domain within Mgm1 is identified.
  • Mgm1's GTPase activity is regulated by interaction with inner mitochondrial membrane lipids.
  • Mgm1 oligomerization and lipid binding are critical for its function in mitochondrial fusion.
  • A structural model for Mgm1-mediated mitochondrial inner membrane fusion is proposed.

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