Molecular Basis of the Interaction between Proapoptotic Truncated BID (tBID) Protein and Mitochondrial Carrier Homologue 2 (MTCH2) Protein

Katz, Chen; Zaltsman-Amir, Yehudit; Mostizky, Yana; Kollet, Neta; Gross, Atan; Friedler, Assaf

doi:10.1074/jbc.m111.328377

Cited by 36 publications

(45 citation statements)

References 34 publications

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“…SMAC was used as a control as it is not affected by salt concentration Cardiolipin or MTCH2 can serve as tBID receptors E Raemy et al such compensatory mechanisms, as previous experiments showed that PG cannot substitute for CL in the regulation of MOMP. 13,27 In contrast, MTCH2, which has previously been reported to act as a tBID receptor, 29,41 could compensate for the CL deficit. In favor of this hypothesis, we observed an effect of MTCH2 depletion on tBID recruitment in cells depleted of CL (Figures 5a and b), suggesting that CL and MTCH2 may have compensatory roles in directly binding and recruiting tBID to the MOM, an idea already proposed by others.…”

Section: Discussionmentioning

confidence: 90%

“…In the light of recent studies indicating that MTCH2 may be a receptor for tBID in the MOM, 29,41 we wished to study the effect of MTCH2 downregulation on tBID recruitment to mitochondria, following induction of cell death in WT and CLS1 KO cells. We found that in cells depleted of MTCH2, tBID was normally recruited to mitochondria upon treatment with TRAIL.…”

Section: Resultsmentioning

confidence: 99%

“…35 Importantly, MTCH2, a protein of the mitochondrial carrier family inserted in the MOM, has been recently proposed to act as a receptor for tBID under apoptotic conditions. 29,41 To test the involvement of CL in apoptosis, we chose to focus on TRAIL-induced apoptosis in HCT116 cells. These cells show a type II response 43 and apoptosis is dependent on tBID and BAX, but not on BAK that is tightly inhibited by MCL-1.…”

Section: Discussionmentioning

confidence: 99%

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Cardiolipin or MTCH2 can serve as tBID receptors during apoptosis

et al. 2016

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During apoptosis, proapoptotic BAX and BAK trigger mitochondrial outer membrane (MOM) permeabilization by a mechanism that is not yet fully understood. BH3-only proteins such as tBID, together with lipids of the MOM, are thought to play a key role in BAX and BAK activation. In particular, cardiolipin (CL) has been shown to stimulate tBID-induced BAX activation in vitro. However, it is still unclear whether this process also relies on CL in the cell, or whether it is more dependent on MTCH2, a proposed receptor for tBID present in the MOM. To address this issue, we deleted both alleles of cardiolipin synthase in human HCT116 cells by homologous recombination, which resulted in a complete absence of CL. The CL-deficient cells were fully viable in glucose but displayed impaired oxidative phosphorylation and an inability to grow in galactose. Using these cells, we found that CL was not required for either tBID-induced BAX activation, or for apoptosis in response to treatment with TRAIL. Downregulation of MTCH2 in HCT116 cells also failed to prevent recruitment of tBID to mitochondria in apoptotic conditions. However, when both CL and MTCH2 were depleted, a significant reduction in tBID recruitment was observed, suggesting that in HCT116 cells, CL and MTCH2 can have redundant functions in this process.

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Section: Discussionmentioning

confidence: 90%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Cardiolipin or MTCH2 can serve as tBID receptors during apoptosis

et al. 2016

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“…53,54 Arrestin-2 does not have mitochondrial localization signal, and mitochondria contain little FL arrestin-2. However, large proportion of 1-380 localizes to mitochondria.…”

Section: Discussionmentioning

confidence: 99%

Caspase-cleaved arrestin-2 and BID cooperatively facilitate cytochrome C release and cell death

et al. 2013

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Apoptosis is programmed cell death triggered by activation of death receptors or cellular stress. Activation of caspases is the hallmark of apoptosis. Arrestins are best known for their role in homologous desensitization of G protein-coupled receptors (GPCRs). Arrestins quench G protein activation by binding to activated phosphorylated GPCRs. Recently, arrestins have been shown to regulate multiple signalling pathways in G protein-independent manner via scaffolding signalling proteins. Here we demonstrate that arrestin-2 isoform is cleaved by caspases during apoptosis induced via death receptor activation or by DNA damage at evolutionarily conserved sites in the C-terminus. Caspase-generated arrestin-2-(1-380) fragment translocates to mitochondria increasing cytochrome C release, which is the key checkpoint in cell death. Cells lacking arrestin-2 are significantly more resistant to apoptosis. The expression of wild-type arrestin-2 or its cleavage product arrestin-2-(1-380), but not of its caspase-resistant mutant, restores cell sensitivity to apoptotic stimuli. Arrestin-2-(1-380) action depends on tBID: at physiological concentrations, arrestin-2-(1-380) directly binds tBID and doubles tBID-induced cytochrome C release from isolated mitochondria. Arrestin-2-(1-380) does not facilitate apoptosis in BID knockout cells, whereas its ability to increase caspase-3 activity and facilitate cytochrome C release is rescued when BID expression is restored. Thus, arrestin-2-(1-380) cooperates with another product of caspase activity, tBID, and their concerted action significantly contributes to cell death.

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“…This extended tBid loop between helices ␣ 4 and ␣ 5 was shown to be highly flexible and did not show any interaction with the micelles, contrasting to the rigid helical conformation in Bid (Figs. 1 and 4) (60), through which tBid can directly interact with the protein MTCH2 (mitochondrial carrier homologue 2) (36,61). The exposure of this flexible tBid loop enables a scenario where the interaction between tBid and MTCH2 is likely to occur at the mitochondria outer membrane.…”

Section: Distance Restraints (å)mentioning

confidence: 99%

Structural Insights of tBid, the Caspase-8-activated Bid, and Its BH3 Domain

Wang

Tjandra

2013

Journal of Biological Chemistry

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Background:The membrane-associated tBid promotes Bax membrane insertion and activation. Results: tBid adopts an extended structure in 1-palmitoyl-2-hydroxy-sn-glycero-3-[phospho-RAC-(1-glycerol)] (LPPG) micelles with its six helices including the BH 3 domain interacting with the micelles. Conclusion: An "on the membrane" binding mode was suggested for tBid interaction with Bax. Significance: Revealing tBid structure on the membrane is key to the understanding of tBid-mediated Bax activation.

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Molecular Basis of the Interaction between Proapoptotic Truncated BID (tBID) Protein and Mitochondrial Carrier Homologue 2 (MTCH2) Protein

Cited by 36 publications

References 34 publications

Cardiolipin or MTCH2 can serve as tBID receptors during apoptosis

Cardiolipin or MTCH2 can serve as tBID receptors during apoptosis

Caspase-cleaved arrestin-2 and BID cooperatively facilitate cytochrome C release and cell death

Structural Insights of tBid, the Caspase-8-activated Bid, and Its BH3 Domain

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