Abstract
Apoptosis is a highly conserved genetic process leading to death in mammalian cells. A critical step in apoptosis is mitochondrial membrane permeabilization, which results in the release of proteins critical to downstream events. Transmembrane protein 14A (TMEM14A) was identified as a novel suppressor of Bax using yeast-based functional screening. TMEM14A is a novel mitochondria-associated membrane protein containing a putative transmembrane domain. Over-expression of TMEM14A in U87MG cells inhibited N-(4-hydroxyphenyl)retinamide (4-HPR)-induced apoptosis. TMEM14A prevented 4-HPR-induced loss of mitochondrial membrane potential (MMP), the release of cytochrome c, and the activation of caspase-3, but not the generation of reactive oxygen species, suggesting that TMEM14A regulates mitochondrial membrane potential in a ROS-independent manner. As expected, cyclosporin A, an inhibitor of membrane potential transition, inhibited 4-HPR-induced loss of MMP and apoptosis in U87MG cells, indicating that loss of MMP plays a pivotal role in 4-HPR-induced apoptosis. Suppression of TMEM14A expression using shRNA significantly increased apoptosis and MMP loss in untreated and 4-HPR-treated cells. These findings show for the first time that TMEM14A inhibits apoptosis by blocking the mitochondrial permeability transition and stabilizing mitochondrial membrane potential.
Original language | English |
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Pages (from-to) | 190-198 |
Number of pages | 9 |
Journal | Cancer letters |
Volume | 309 |
Issue number | 2 |
DOIs | |
Publication status | Published - 2011 Oct 28 |
Externally published | Yes |
Bibliographical note
Funding Information:This research was supported in part by Basic Science Research Program ( 2010-0012064 ) and MRC Program ( 2011-0006200 ) through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology .
Keywords
- Apoptosis
- Glioblastoma
- Mitochondria membrane potential
- TMEM14A
ASJC Scopus subject areas
- Oncology
- Cancer Research