Systematic mapping of contact sites reveals tethers and a function for the peroxisome-mitochondria contact

Nadav Shai (1) , Eden Yifrach (1) , Carlo W. T. van Roermund (2) , Nir Cohen (1) , Chen Bibi (1) , Lodewijk Ijlst (2) , Laetitia Cavellini (3) , Julie Meurisse (3) , Ramona Schuster (4) , Lior Zada (1) , Muriel C. Mari (5) , Fulvio M. Reggiori (5) , Adam L. Hughes (6) , Mafalda Escobar-Henriques (4) , Mickaël Cohen (3) , Hans R. Waterham (2) , Ronald J. A. Wanders (2) , Maya Schuldiner (1) , Einat Zalckvar (1)

1 Weizmann Institute of Science [Rehovot, Israël]
2 UvA - University of Amsterdam [Amsterdam] = Universiteit van Amsterdam
3 LBMCE - Laboratoire de Biologie Moléculaire et Cellulaire des Eucaryotes
4 University of Cologne
5 UMCG - University Medical Center Groningen [Groningen]
6 School of Medicine [University of Utah, Salt Lake City]

The understanding that organelles are not floating in the cytosol, but rather held in an organized yet dynamic interplay through membrane contact sites, is altering the way we grasp cell biological phenomena. However, we still have not identified the entire repertoire of contact sites, their tethering molecules and functions. To systematically characterize contact sites and their tethering molecules here we employ a proximity detection method based on split fluorophores and discover four potential new yeast contact sites. We then focus on a little-studied yet highly disease-relevant contact, the Peroxisome-Mitochondria (PerMit) proximity, and uncover and characterize two tether proteins: Fzo1 and Pex34. We genetically expand the PerMit contact site and demonstrate a physiological function in β-oxidation of fatty acids. Our work showcases how systematic analysis of contact site machinery and functions can deepen our understanding of these structures in health and disease.

Mots clés: High-throughput screening; Mitochondria; Organelles; Peroxisomes

Domaines: Organisation et fonctions cellulaires [q-bio.SC]

Nadav Shai, Eden Yifrach, Carlo W. T. van Roermund, Nir Cohen, Chen Bibi, et al.. Systematic mapping of contact sites reveals tethers and a function for the peroxisome-mitochondria contact. Nature Communications, 2018, 9, pp.1761. ⟨10.1038/s41467-018-03957-8⟩. ⟨hal-01959227⟩