Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul, Korea.
PLoS One. 2010 Sep 2;5(9):e12535. doi: 10.1371/journal.pone.0012535.
Leucine zipper/EF hand-containing transmembrane-1 (LETM1) encodes for the human homologue of yeast Mdm38p, which is a mitochondria-shaping protein of unclear function. However, a previous study demonstrated that LETM1 served as an anchor protein for complex formation between mitochondria and ribosome, and regulated mitochondrial biogenesis.
METHODOLOGY/PRINCIPAL FINDINGS: Therefore, we examine the possibility that LETM1 may function to regulate mitochondria and lung tumor growth. In this study, we addressed this question by studying in the effect of adenovirus-mediated LETM1 in the lung cancer cell and lung cancer model mice. To investigate the effects of adenovirus-LETM1 in vitro, we infected with adenovirus-LETM1 in A549 cells. Additionally, in vivo effects of LETM1 were evaluated on K-ras(LA1) mice, human non-small cell lung cancer model mice, by delivering the LETM1 via aerosol through nose-only inhalation system. The effects of LETM1 on lung cancer growth and AMPK related signals were evaluated. Adenovirus-mediated overexpression of LETM1 could induce destruction of mitochondria of lung cancer cells through depleting ATP and AMPK activation. Furthermore, adenoviral-LETM1 also altered Akt signaling and inhibited the cell cycle while facilitating apoptosis. Theses results demonstrated that adenovirus-LETM1 suppressed lung cancer cell growth in vitro and in vivo.
CONCLUSIONS/SIGNIFICANCE: Adenovirus-mediated LETM1 may provide a useful target for designing lung tumor prevention and treatment.
亮氨酸拉链/EF 手跨膜结构域 1（LETM1）编码酵母 Mdm38p 的人类同源物，后者是一种功能不明的线粒体成形蛋白。然而，先前的研究表明 LETM1 作为线粒体与核糖体形成复合物的锚定蛋白，并调节线粒体生物发生。
方法/主要发现：因此，我们研究了 LETM1 可能调节线粒体和肺肿瘤生长的可能性。在这项研究中，我们通过研究腺病毒介导的 LETM1 在肺癌细胞和肺癌模型小鼠中的作用来解决这个问题。为了研究腺病毒-LETM1 在体外的作用，我们用腺病毒-LETM1 感染 A549 细胞。此外，通过鼻内吸入系统通过鼻腔给予 LETM1，在 K-ras（LA1）小鼠、人非小细胞肺癌模型小鼠中评估 LETM1 的体内作用。评估 LETM1 对肺癌生长和 AMPK 相关信号的影响。腺病毒介导的 LETM1 过表达可通过耗尽 ATP 和激活 AMPK 诱导肺癌细胞中线粒体的破坏。此外，腺病毒-LETM1 还改变了 Akt 信号传导并抑制了细胞周期，同时促进了细胞凋亡。这些结果表明腺病毒介导的 LETM1 可抑制体外和体内肺癌细胞的生长。
结论/意义：腺病毒介导的 LETM1 可能为设计肺肿瘤的预防和治疗提供有用的靶点。
