Mitofusin-mediated contacts between mitochondria and peroxisomes regulate mitochondrial fusion

Cynthia Alsayyah, Manish K Singh, Maria Angeles Morcillo-Parra, Laetitia Cavellini, Nadav Shai, Christine Schmitt, Maya Schuldiner, Einat Zalckvar, Adeline Mallet, Naïma Belgareh-Touzé, Christophe Zimmer and Mickaël M Cohen

PLOS Biology, 2024, vol. 22, issue 4, 1-37

Abstract: 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.The yeast mitofusin Fzo1 naturally localizes to peroxisomes to promote their tethering with mitochondria, but the physiological relevance of this contact is unclear. Here, the authors show that these Fzo1-mediated PerMit contacts are required to maintain mitochondrial fusion as fatty acid desaturation increases.

Date: 2024
References: View complete reference list from CitEc
Citations:

Downloads: (external link)
https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3002602 (text/html)
https://journals.plos.org/plosbiology/article/file ... 02602&type=printable (application/pdf)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:plo:pbio00:3002602

DOI: 10.1371/journal.pbio.3002602

Access Statistics for this article

More articles in PLOS Biology from Public Library of Science
Bibliographic data for series maintained by plosbiology ().