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

L.Z. Piao, Y.W. Li, S.J. Kim, K.C. Sohn, K.J. Yang, Y.A. Park, H.S. Byun, M.H. Won, J.H. Hong, G.M. Hur, J.H. Seok, M.H. Shong, R. Sack, Derek Brazil, B.A. Hemmings, J. Park

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Abstract

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. (C) 2009 Elsevier Inc. All rights reserved
Original languageEnglish
Pages (from-to)767-777
Number of pages11
JournalCellular Signalling
Volume21
Issue number5
DOIs
Publication statusPublished - May 2009

ASJC Scopus subject areas

  • Cell Biology

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    Piao, L. Z., Li, Y. W., Kim, S. J., Sohn, K. C., Yang, K. J., Park, Y. A., Byun, H. S., Won, M. H., Hong, J. H., Hur, G. M., Seok, J. H., Shong, M. H., Sack, R., Brazil, D., Hemmings, B. A., & Park, J. (2009). Regulation of OPA1-mediated mitochondrial fusion by leucine zipper/EF-hand-containing transmembrane protein-1 plays a role in apoptosis. Cellular Signalling, 21(5), 767-777. https://doi.org/10.1016/j.cellsig.2009.01.020