title: Regulation of OPA1-mediated mitochondrial fusion by leucine zipper/EF-hand-containing transmembrane protein-1 plays a role in apoptosis.
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.
authors.affiliation: 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.
authors.forename: Longzhen
authors.initials: L
authors.lastname: Piao
authors.forename: Yuwen
authors.initials: Y
authors.lastname: Li
authors.forename: Soung Jung
authors.initials: SJ
authors.lastname: Kim
authors.forename: Kyung-Cheol
authors.initials: KC
authors.lastname: Sohn
authors.forename: Keum-Jin
authors.initials: KJ
authors.lastname: Yang
authors.forename: Kyeong Ah
authors.initials: KA
authors.lastname: Park
authors.forename: Hee Sun
authors.initials: HS
authors.lastname: Byun
authors.forename: Minho
authors.initials: M
authors.lastname: Won
authors.forename: Janghee
authors.initials: J
authors.lastname: Hong
authors.forename: Gang Min
authors.initials: GM
authors.lastname: Hur
authors.forename: Jeong Ho
authors.initials: JH
authors.lastname: Seok
authors.forename: Minho
authors.initials: M
authors.lastname: Shong
authors.forename: Ragna
authors.initials: R
authors.lastname: Sack
authors.forename: Derek P
authors.initials: DP
authors.lastname: Brazil
authors.forename: Brian A
authors.initials: BA
authors.lastname: Hemmings
authors.forename: Jongsun
authors.initials: J
authors.lastname: Park
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D017209:Apoptosis; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002460:Cell Line; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D013869:Thiolester Hydrolases
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002135:Calcium-Binding Proteins; C488528:LETM1 protein, human; D008565:Membrane Proteins; D000255:Adenosine Triphosphate; C437985:THEM4 protein, human; D013869:Thiolester Hydrolases; D020558:GTP Phosphohydrolases; C415198:OPA1 protein, human