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Association of LETM1 and MRPL36 Contributes to the Regulation of Mitochondrial ATP Production and Necrotic Cell Death

Cited 53 time in Web of Science Cited 56 time in Scopus
Authors
Piao, Longzhen; Li, Yuwen; Kim, Soung Jung; Byun, Hee Sun; Huang, Song Mei; Hwang, Soon-Kyung; Yang, Keum-Jin; Park, Kyeong Ah; Won, Minho; Hong, Janghee; Hur, Gang Min; Seok, Jeong Ho; Shong, Minho; Cho, Myung-Haing; Brazil, Derek P.; Hemmings, Brian A.; Park, Jongsun
Issue Date
2009-04
Citation
Cancer Research, Vol.69 No.8, pp.3397-3404
Abstract
Leucine zipper/EF hand-containing transmembrane-1 (LETM1) is a mitochondrial inner membrane protein that was first identified in Wolf-Hirschhorn syndrome, and was deleted in nearly all patients with the syndrome. LETM1 encodes for the human homologue of yeast Mdm38p, which is a mitochondria-shaping protein of unclear function. Here, we describe LETM1-mediated regulation of mitochondrial ATP production and biogenesis. We show that LETM1 overexpression can induce necrotic cell death in HeLa cells, in which LETM1 reduces mitochondria) biogenesis and ATP production. LETM1 acts as an anchor protein and associates with mitochondrial ribosome protein L36. Adenovirus-mediated overexpression of LETM1 reduced mitochondrial mass and expression of many mitochondrial proteins. LETM1-mediated inhibition of mitochondrial biogenesis enhanced glycolytic ATP supply and activated protein kinase B activity and cell survival signaling. The expression levels of LETM1 were significantly increased in multiple human cancer tissues compared with normals. These data suggest that LETM1 serves as an anchor protein for complex formation with the mitochondrial ribosome and regulates mitochondrial biogenesis. The increased expression of LETM1 in human cancer suggests that deregulation of LETM1 is a key feature of tumorigenesis. [Cancer Res 2009;69(8):3397-404]
ISSN
0008-5472
URI
https://hdl.handle.net/10371/172356
DOI
https://doi.org/10.1158/0008-5472.CAN-08-3235
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College of Veterinary Medicine (수의과대학)Dept. of Veterinary Medicine (수의학과)Journal Papers (저널논문_수의학과)
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