Regulation of OPA1-mediated mitochondrial fusion by leucine zipper/EF-hand-containing transmembrane protein-1 plays a role in apoptosis |
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| Authors: | Longzhen Piao Yuwen Li Soung Jung Kim Kyung-Cheol Sohn Keum-Jin Yang Kyeong Ah Park Hee Sun Byun Minho Won Janghee Hong Gang Min Hur Jeong Ho Seok Minho Shong Ragna Sack Derek P. Brazil Brian A. Hemmings Jongsun Park |
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| Affiliation: | 1. Department of Pharmacology, Daejeon Regional Cancer Center, Cancer Research Institute, Research Institute for Medical Sciences, College of Medicine, Chungnam National University, Taejeon, 301-131, Republic of Korea;2. Department of Internal Medicine, College of Medicine, Chungnam National University, Taejeon, 301-131, Republic of Korea;3. Department of Dermatology, College of Medicine, Chungnam National University, Taejeon, 301-131, Republic of Korea;4. Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland;5. UCD Diabetes Research Centre, UCD Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland;1. Taras Shevchenko National University of Kyiv, Faculty of Cybernetics, Volodymyrska str. 64, 01030 Kyiv, Ukraine;2. Taras Shevchenko National University of Kyiv, The Institute of Biology, Volodymyrska str. 64, 01030 Kyiv, Ukraine;1. Division of Pediatric Neurology and Inborn Errors of Metabolism, Department of Pediatrics, University Hospital Heidelberg, Ruprecht-Karls-University Heidelberg, Heidelberg, Germany;2. Department of Neuroradiology, Heidelberg University Hospital, Ruprecht-Karls-University Heidelberg, Heidelberg, Germany;1. Yonsei Biomedical Research Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Korea;1. Department of Psychology, Michigan State University, East Lansing, MI, USA;2. Department of Biological Sciences, Western Michigan University, Kalamazoo, MI, USA;3. Department of Psychology, Hope College, Holland, MI, USA;3. Mitochondrial Function, Nestlé Institute of Health Sciences, EPFL Innovation Park, Building G, CH-1015 Lausanne, Switzerland;4. Department of Cell Physiology and Metabolism, University of Geneva, Rue Michel-Servet, 1, CH-1211 Genève, Switzerland;5. Department of Physiology, Ben-Gurion University of Negev, Beer-Sheva 84105, Israel |
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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. |
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