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

Abstract

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.

Peroxisomal fission is modulated by the mitochondrial Rho‐GTPases, Miro1 and Miro2

“…Furthermore, building a model for Miro in modulating peroxisomal morphology should also consider that Castro et al [34,52] proposed that Miro1 might promote peroxisomal elongation through coupling to microtubules. For example, Gem1 (the yeast orthologue of Miro) has been identified as a potential regulator of mitochondria-peroxisome contact sites [68]. For example, Gem1 (the yeast orthologue of Miro) has been identified as a potential regulator of mitochondria-peroxisome contact sites [68].…”

Peroxisome biogenesis, membrane contact sites, and quality control

“…The existence of sites of close proximity between the peroxisomes and mitochondria was confirmed by bimolecular fluorescence complementation (BiFC) in S. cerevisiae tagging three different peroxins (Pex3, Pex11, and Pex25) and two mitochondrial (Tom70 and Tom20) reporters [165]. Overexpression of Pex34 (the closest homologue to P. pastoris Pex36 and mammalian PEX16) or Fzo1 (a yeast mitofusin protein) enhanced the number of contact sites.…”

“…Surprisingly, deletion of the yeast PEX34 and PEX11 genes did not alter the number of contact sites observed by BiFC [165]. However, lack of Pex11, a PMP implicated in MCS with mitochondria, reduced the colocalization between a mitochondrial component of the ERMES (ER-mitochondrial encounter structures) complex, Mdm34 (Mdm34-mCherry), and Pex14-GFP [150]).…”

Silencing of OsCV (chloroplast vesiculation) maintained photorespiration and N assimilation in rice plants grown under elevated CO2

“…Interestingly, in addition to maintaining chloroplast stability (Sade et al, ) and the number of peroxisomes, CV ‐silenced plants also maintained a higher number of mitochondria than WT plants under elevated CO 2 (Figure ). In yeast, the physical interaction between mitochondria and peroxisomes has been demonstrated, that is, Pex11/Mdm34 (Mattiazzi et al, ) and Pex34/Fzo1(Shai et al, ). In plants, Oikawa et al () used in situ laser analysis to demonstrate the physical interaction between chloroplasts, peroxisomes, and mitochondria.…”