Mitofusin-mediated contacts between mitochondria and peroxisomes regulate mitochondrial fusion.

Mitofusins are large GTPases that trigger fusion of mitochondrial outer membranes. Similarly to the human mitofusin Mfn2, which also tethers mitochondria to the endoplasmic reticulum (ER), the yeast mitofusin Fzo1 stimulates contacts between Peroxisomes and Mitochondria when overexpressed. Yet, the physiological significance and function of these "PerMit" contacts remain unknown. ...
Here, we demonstrate that Fzo1 naturally localizes to peroxisomes and promotes PerMit contacts in physiological conditions. These contacts are regulated through co-modulation of Fzo1 levels by the ubiquitin-proteasome system (UPS) and by the desaturation status of fatty acids (FAs). Contacts decrease under low FA desaturation but reach a maximum during high FA desaturation. High-throughput genetic screening combined with high-resolution cellular imaging reveal that Fzo1-mediated PerMit contacts favor the transit of peroxisomal citrate into mitochondria. In turn, citrate enters the TCA cycle to stimulate the mitochondrial membrane potential and maintain efficient mitochondrial fusion upon high FA desaturation. These findings thus unravel a mechanism by which inter-organelle contacts safeguard mitochondrial fusion.
Mesh Terms:
Citric Acid Cycle, Endoplasmic Reticulum, Fatty Acids, GTP Phosphohydrolases, Humans, Membrane Potential, Mitochondrial, Membrane Proteins, Mitochondria, Mitochondrial Dynamics, Mitochondrial Membranes, Mitochondrial Proteins, Peroxisomes, Proteasome Endopeptidase Complex, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins
PLoS Biol
Date: Apr. 01, 2024
Download Curated Data For This Publication
250046
Switch View:
  • Interactions 4