Regulation of OPA1-mediated mitochondrial fusion by leucine zipper/EF-hand-containing transmembrane protein-1 plays a role in apoptosis

Cell Signal. 2009 May;21(5):767-77. doi: 10.1016/j.cellsig.2009.01.020. Epub 2009 Jan 9.


Carboxyl-terminal modulator protein (CTMP) is a tumor suppressor-like binding partner of Protein kinase B (PKB/Akt) that negative regulates this kinase. In the course of our recent work, we identified that CTMP is consistently associated with leucine zipper/EF-hand-containing transmembrane-1 (LETM1). Here, we report that adenovirus-LETM1 increased the sensitivity of HeLa cells to apoptosis, induced by either staurosporine or actinomycin D. As shown previously, LETM1 localized to the inner mitochondrial membrane. Electron-microscopy analysis of adenovirus-LETM1 transduced cells revealed that mitochondrial cristae were swollen in these cells, a phenotype similar to that observed in optic atrophy type-1 (OPA1)-ablated cells. OPA1 cleavage was increased in LETM1-overexpressing cells, and this phenotype was reversed by overexpression of OPA1 variant-7, a cleavage resistant form of OPA1. Taken together, these data suggest that LETM1 is a novel binding partner for CTMP that may play an important role in mitochondrial fragmentation via OPA1-cleavage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Adenosine Triphosphate / metabolism
  • Apoptosis*
  • Calcium-Binding Proteins / metabolism*
  • Cell Line
  • GTP Phosphohydrolases / metabolism*
  • HeLa Cells
  • Humans
  • Membrane Proteins / metabolism*
  • Mitochondria / metabolism*
  • Mitochondria / ultrastructure
  • Thiolester Hydrolases


  • Adaptor Proteins, Signal Transducing
  • Calcium-Binding Proteins
  • LETM1 protein, human
  • Membrane Proteins
  • Adenosine Triphosphate
  • THEM4 protein, human
  • Thiolester Hydrolases
  • GTP Phosphohydrolases
  • OPA1 protein, human