Endoplasmic reticulum-associated mitochondria-cortex tether functions in the distribution and inheritance of mitochondria

Proc Natl Acad Sci U S A. 2013 Feb 5;110(6):E458-67. doi: 10.1073/pnas.1215232110. Epub 2013 Jan 22.

Abstract

To elucidate the functional roles of mitochondrial dynamics in vivo, we identified genes that become essential in cells lacking the dynamin-related proteins Fzo1 and Dnm1, which are required for mitochondrial fusion and division, respectively. The screen identified Num1, a cortical protein implicated in mitochondrial division and distribution that also functions in nuclear migration. Our data indicate that Num1, together with Mdm36, forms a physical tether that robustly anchors mitochondria to the cell cortex but plays no direct role in mitochondrial division. Our analysis indicates that Num1-dependent anchoring is essential for distribution of the static mitochondrial network in fzo1 dnm1 cells. Consistently, expression of a synthetic mitochondria-cortex tether rescues the viability of fzo1 dnm1 num1 cells. We find that the cortical endoplasmic reticulum (ER) also is a constituent of the Num1 mitochondria-cortex tether, suggesting an active role for the ER in mitochondrial positioning in cells. Thus, taken together, our findings identify Num1 as a key component of a mitochondria-ER-cortex anchor, which we termed "MECA," that functions in parallel with mitochondrial dynamics to distribute and position the essential mitochondrial network.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cytoskeletal Proteins / chemistry
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism
  • Endoplasmic Reticulum / metabolism*
  • GTP Phosphohydrolases / genetics
  • GTP Phosphohydrolases / metabolism
  • Genes, Fungal
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mitochondria / genetics*
  • Mitochondria / metabolism*
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism
  • Models, Biological
  • Mutation
  • Protein Structure, Tertiary
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism

Substances

  • Cytoskeletal Proteins
  • Mdm36 protein, S cerevisiae
  • Membrane Proteins
  • Mitochondrial Proteins
  • NUM1 protein, S cerevisiae
  • Recombinant Fusion Proteins
  • Saccharomyces cerevisiae Proteins
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins
  • FZO1 protein, S cerevisiae
  • GTP Phosphohydrolases
  • DNM1 protein, S cerevisiae