Mitofusin-mediated contacts between mitochondria and peroxisomes regulate mitochondrial fusion

Cynthia Alsayyah1, Manish K Singh1,2, Maria Angeles Morcillo-Parra1

  • 1Laboratoire de Biologie Moléculaire et Cellulaire des Eucaryotes, Sorbonne Université, CNRS, UMR8226, Institut de Biologie Physico-Chimique, Paris, France.

Plos Biology
|April 26, 2024
PubMed

Insights

Yeast mitofusins (Fzo1) create peroxisome-mitochondria contacts, crucial for cell function. These contacts regulate citrate transport, maintaining mitochondrial fusion during fatty acid desaturation.

Area of Science:

  • Cell Biology
  • Mitochondrial Dynamics
  • Organelle Contact Sites

Background:

  • Mitofusins are GTPases essential for mitochondrial outer membrane fusion.
  • Yeast Fzo1, a mitofusin, induces peroxisome-mitochondria (PerMit) contacts upon overexpression.
  • The physiological role of PerMit contacts remains unclear.

Purpose of the Study:

  • To investigate the physiological role of Fzo1 in PerMit contacts.
  • To understand the regulation and function of Fzo1-mediated PerMit contacts.

Main Methods:

  • Yeast genetics and high-resolution cellular imaging.
  • High-throughput genetic screening.
  • Analysis of Fzo1 protein levels and fatty acid desaturation.

Main Results:

  • Fzo1 naturally localizes to peroxisomes, promoting PerMit contacts under physiological conditions.
  • Fzo1 levels are regulated by the ubiquitin-proteasome system (UPS) and fatty acid (FA) desaturation status.
  • PerMit contacts are maximal during high FA desaturation and facilitate peroxisomal citrate export to mitochondria.
  • Mitochondrial citrate import boosts the TCA cycle, enhancing membrane potential and mitochondrial fusion.

Conclusions:

  • Fzo1-mediated PerMit contacts are physiologically relevant and regulated by UPS and FA desaturation.
  • These contacts enable citrate transfer from peroxisomes to mitochondria, supporting mitochondrial fusion.
  • Inter-organelle contacts serve as a mechanism to maintain mitochondrial integrity.

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