Intramitochondrial recruitment of endolysosomes mediates Smac degradation and constitutes a novel intrinsic apoptosis antagonizing function of XIAP E3 ligase. (Cell Death and Differentiation 2014, 1-15)

報告日期: 2014/10/03
報告時間: 4:00/4:50
報告學生: 鍾校木
講評老師: 洪良宜
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Intramitochondrial recruitment of endolysosomes mediates Smac degradation and constitutes a novel intrinsic apoptosis antagonizing function of XIAP E3 ligase

Cell Death and Differentiation (2014),1-15

Name : 鍾校木                                        Class : Room 602

Commentator : 洪良宜老師                            Date : 2014-10-3

 

  In intrinsic apoptosis, BH3-protein can induce mitochondria outer membrane permeabilization (MMOP), leading to the release of cytochrome c to the cytoplasm to activate caspase-dependent cell death. On the other hand, it has been shown that damaged or dysfunction mitochondria can be targeted to lysosome and subsequently be degraded though autophagy pathway. However, the mechanism and correlation between autophagy and apoptosis are unclear. In this study, authors found a novel function and mechanism of canonical BH3-only proteins and XIAP, an IAP family protein, in regulating molecules in the damaged mitochondria. Overexpression of the canonical BH3-only proteins, tBid, BimEL, Bik, Bad and LIR-mutated atypical BH3-only protein, Bnip3 and Nix, was shown to induce the recruitment of endolysosome to mitochondria without triggering mitophagy induction. In addition, XIAP, an IAP family protein that can inhibit apoptosis though interact with caspase protein, was shown to translocate to the dysfunction mitochondria rapidly after mitochondrial depolarization. Findings of this study also revealed that XIAP actuated MOMP within mitochondria and triggered ubiquitin-dependent recruitment of Rab proteins that were located within the XIAP-target mitochondria. Interestingly, XIAP also promoted the degradation of its negative regulator, Smac, though lysosomal and proteasomal pathways in the mitochondria. These findings suggest that XIAP-mediated intramitochondria degradation of Smac though lysosomal and proteasomal represents a new apoptosis checkpoint signaling, which provide a novelty mechanism to lower the mitochondrial apoptotic activation.

Key words: Canonical BH3-protein, lysosomal, XIAP, ubiquitylation, Smac

 

References

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