TMEM14A inhibits N-(4-hydroxyphenyl)retinamide-induced apoptosis through the stabilization of mitochondrial membrane potential

Im Sun Woo, Hana Jin, Eun Sil Kang, Hye Jung Kim, Jae Heun Lee, Ki Churl Chang, Jae-Yong Park, Wan Sung Choi, Han Geuk Seo

Research output: Contribution to journalArticle

22 Citations (Scopus)

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 languageEnglish
Pages (from-to)190-198
Number of pages9
JournalCancer letters
Volume309
Issue number2
DOIs
Publication statusPublished - 2011 Oct 28
Externally publishedYes

Fingerprint

Fenretinide
Mitochondrial Membrane Potential
Apoptosis
Proteins
Genetic Phenomena
Mitochondrial Membranes
Cytochromes c
Caspase 3
Membrane Potentials
Small Interfering RNA
Cyclosporine
Permeability
Reactive Oxygen Species
Mitochondria
Membrane Proteins
Yeasts

Keywords

  • Apoptosis
  • Glioblastoma
  • Mitochondria membrane potential
  • TMEM14A

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

TMEM14A inhibits N-(4-hydroxyphenyl)retinamide-induced apoptosis through the stabilization of mitochondrial membrane potential. / Woo, Im Sun; Jin, Hana; Kang, Eun Sil; Kim, Hye Jung; Lee, Jae Heun; Chang, Ki Churl; Park, Jae-Yong; Choi, Wan Sung; Seo, Han Geuk.

In: Cancer letters, Vol. 309, No. 2, 28.10.2011, p. 190-198.

Research output: Contribution to journalArticle

Woo, Im Sun ; Jin, Hana ; Kang, Eun Sil ; Kim, Hye Jung ; Lee, Jae Heun ; Chang, Ki Churl ; Park, Jae-Yong ; Choi, Wan Sung ; Seo, Han Geuk. / TMEM14A inhibits N-(4-hydroxyphenyl)retinamide-induced apoptosis through the stabilization of mitochondrial membrane potential. In: Cancer letters. 2011 ; Vol. 309, No. 2. pp. 190-198.
@article{91aae08df7ed4071a191e7c1e6acf956,
title = "TMEM14A inhibits N-(4-hydroxyphenyl)retinamide-induced apoptosis through the stabilization of mitochondrial membrane potential",
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.",
keywords = "Apoptosis, Glioblastoma, Mitochondria membrane potential, TMEM14A",
author = "Woo, {Im Sun} and Hana Jin and Kang, {Eun Sil} and Kim, {Hye Jung} and Lee, {Jae Heun} and Chang, {Ki Churl} and Jae-Yong Park and Choi, {Wan Sung} and Seo, {Han Geuk}",
year = "2011",
month = "10",
day = "28",
doi = "10.1016/j.canlet.2011.05.031",
language = "English",
volume = "309",
pages = "190--198",
journal = "Cancer Letters",
issn = "0304-3835",
publisher = "Elsevier Ireland Ltd",
number = "2",

}

TY - JOUR

T1 - TMEM14A inhibits N-(4-hydroxyphenyl)retinamide-induced apoptosis through the stabilization of mitochondrial membrane potential

AU - Woo, Im Sun

AU - Jin, Hana

AU - Kang, Eun Sil

AU - Kim, Hye Jung

AU - Lee, Jae Heun

AU - Chang, Ki Churl

AU - Park, Jae-Yong

AU - Choi, Wan Sung

AU - Seo, Han Geuk

PY - 2011/10/28

Y1 - 2011/10/28

N2 - 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.

AB - 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.

KW - Apoptosis

KW - Glioblastoma

KW - Mitochondria membrane potential

KW - TMEM14A

UR - http://www.scopus.com/inward/record.url?scp=79960835665&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79960835665&partnerID=8YFLogxK

U2 - 10.1016/j.canlet.2011.05.031

DO - 10.1016/j.canlet.2011.05.031

M3 - Article

C2 - 21723035

AN - SCOPUS:79960835665

VL - 309

SP - 190

EP - 198

JO - Cancer Letters

JF - Cancer Letters

SN - 0304-3835

IS - 2

ER -