MOAP-1 Mediates Fas-Induced Apoptosis in Liver by Facilitating tBid Recruitment to Mitochondria

Autor: Chong Teik Tan, Qi-Ling Zhou, Yu-Chin Su, Nai Yang Fu, Hao-Chun Chang, Ran N. Tao, Sunil K. Sukumaran, Shairaz Baksh, Yee-Joo Tan, Kanaga Sabapathy, Chun-Dong Yu, Victor C. Yu
Jazyk: angličtina
Rok vydání: 2016
Předmět:
Zdroj: Cell Reports, Vol 16, Iss 1, Pp 174-185 (2016)
Druh dokumentu: article
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2016.05.068
Popis: Fas apoptotic signaling regulates diverse physiological processes. Acute activation of Fas signaling triggers massive apoptosis in liver. Upon Fas receptor stimulation, the BH3-only protein Bid is cleaved into the active form, tBid. Subsequent tBid recruitment to mitochondria, which is facilitated by its receptor MTCH2 at the outer mitochondrial membrane (OMM), is a critical step for commitment to apoptosis via the effector proteins Bax or Bak. MOAP-1 is a Bax-binding protein enriched at the OMM. Here, we show that MOAP-1-deficient mice are resistant to Fas-induced hepatocellular apoptosis and lethality. In the absence of MOAP-1, mitochondrial accumulation of tBid is markedly impaired. MOAP-1 binds to MTCH2, and this interaction appears necessary for MTCH2 to engage tBid. These findings reveal a role for MOAP-1 in Fas signaling in the liver by promoting MTCH2-mediated tBid recruitment to mitochondria.
Databáze: Directory of Open Access Journals