Num1 anchors mitochondria to the plasma membrane via two domains with different lipid binding specificities

J Cell Biol. 2016 Jun 6;213(5):513-24. doi: 10.1083/jcb.201511021. Epub 2016 May 30.


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.

MeSH terms

  • Cardiolipins / metabolism
  • Cell Membrane / metabolism*
  • Cytoskeletal Proteins / chemistry*
  • Cytoskeletal Proteins / metabolism*
  • Endoplasmic Reticulum / metabolism
  • Lipids / chemistry*
  • Mitochondria / metabolism*
  • Mitochondrial Membranes / metabolism
  • Mitochondrial Proteins / metabolism
  • Phospholipids / metabolism
  • Protein Binding
  • Protein Domains
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / chemistry*
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Structure-Activity Relationship
  • Substrate Specificity


  • Cardiolipins
  • Cytoskeletal Proteins
  • Lipids
  • Mdm36 protein, S cerevisiae
  • Mitochondrial Proteins
  • NUM1 protein, S cerevisiae
  • Phospholipids
  • Saccharomyces cerevisiae Proteins