Regulation of OPA1-mediated mitochondrial fusion by leucine zipper/EF-hand-containing transmembrane protein-1 plays a role in apoptosis.
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.
Piao
Longzhen
L
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.
Li
Yuwen
Y
Kim
Soung Jung
SJ
Sohn
Kyung-Cheol
KC
Yang
Keum-Jin
KJ
Park
Kyeong Ah
KA
Byun
Hee Sun
HS
Won
Minho
M
Hong
Janghee
J
Hur
Gang Min
GM
Seok
Jeong Ho
JH
Shong
Minho
M
Sack
Ragna
R
Brazil
Derek P
DP
Hemmings
Brian A
BA
Park
Jongsun
J
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
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