title: Num1 anchors mitochondria to the plasma membrane via two domains with different lipid binding specificities.
abstract: The mitochondria-ER cortex anchor (MECA) is required for proper mitochondrial distribution and functions by tethering mitochondria to the plasma membrane. The core component of MECA is the multidomain protein Num1, which assembles into clusters at the cell cortex. We show Num1 adopts an extended, polarized conformation. Its N-terminal coiled-coil domain (Num1CC) is proximal to mitochondria, and the C-terminal pleckstrin homology domain is associated with the plasma membrane. We find that Num1CC interacts directly with phospholipid membranes and displays a strong preference for the mitochondria-specific phospholipid cardiolipin. This direct membrane interaction is critical for MECA function. Thus, mitochondrial anchoring is mediated by a protein that interacts directly with two different membranes through lipid-specific binding domains, suggesting a general mechanism for interorganelle tethering.
authors.affiliation: Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208.
authors.forename: Holly A
authors.initials: HA
authors.lastname: Ping
authors.affiliation: Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208.
authors.forename: Lauren M
authors.initials: LM
authors.lastname: Kraft
authors.affiliation: Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208.
authors.forename: WeiTing
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208.
authors.forename: Amy E
authors.initials: AE
authors.lastname: Nilles
authors.affiliation: Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208 laura.lackner@northwestern.edu.
authors.forename: Laura L
authors.initials: LL
authors.lastname: Lackner
mesh_terms: D002308:Cardiolipins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000737:chemistry* / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D008055:Lipids / Q000737:chemistry*; D008928:Mitochondria / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D011485:Protein Binding; D000072417:Protein Domains; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D002308:Cardiolipins; D003598:Cytoskeletal Proteins; D008055:Lipids; C552950:Mdm36 protein, S cerevisiae; D024101:Mitochondrial Proteins; C071961:NUM1 protein, S cerevisiae; D010743:Phospholipids; D029701:Saccharomyces cerevisiae Proteins