Direct membrane binding and self-interaction contribute to Mmr1 function in mitochondrial inheritance.

Area of Science:

• Cell Biology
• Molecular Biology
• Biochemistry

Background:

• Mitochondria are dynamic organelles requiring precise positioning for cellular function.
• In yeast, the Mmr1 protein is essential for transporting and anchoring mitochondria to the bud tip via Myo2.
• The molecular mechanisms underlying Mmr1's interaction with mitochondria remain largely uncharacterized.

Purpose of the Study:

• To elucidate the molecular basis of the Mmr1-mitochondria interaction.
• To identify the specific domains and mechanisms by which Mmr1 binds to and anchors mitochondria.
• To understand the functional significance of Mmr1's membrane binding and self-interaction in mitochondrial inheritance.

Main Methods:

• In vitro phospholipid binding assays to assess Mmr1-membrane interactions.
• Structure-function analyses to identify critical Mmr1 domains (amino acids 76-195 and coiled-coil domain).
• In vivo and in vitro experiments using liposomes to validate Mmr1-mitochondria and Mmr1-membrane interactions.

Main Results:

• Mmr1 directly interacts with phospholipid membranes.
• An unpredicted membrane-binding domain (amino acids 76-195) was identified as necessary and sufficient for Mmr1-mitochondria interaction.
• The coiled-coil domain of Mmr1 is essential for self-interaction and polarized localization.
• Disruption of Mmr1-membrane or Mmr1 self-interaction leads to mitochondrial inheritance defects.

Conclusions:

• Mmr1 utilizes direct membrane binding and self-interaction to anchor mitochondria.
• These interactions are critical for the proper spatial and temporal regulation of mitochondrial positioning.
• Mmr1's dual interaction mechanisms are indispensable for successful mitochondrial inheritance in yeast.