Faculty Opinions recommendation of Caspase cleavage product of BAP31 induces mitochondrial fission through endoplasmic reticulum calcium signals, enhancing cytochrome c release to the cytosol.

2003 ◽  
Author(s):  
Richard Youle
Keyword(s):  
Endoplasmic Reticulum ◽  
Cytochrome C ◽  
Mitochondrial Fission ◽  
Cleavage Product ◽  
Cytochrome C Release ◽  
Calcium Signals ◽  
Caspase Cleavage ◽  
Endoplasmic Reticulum Calcium

scholarly journals Caspase cleavage product of BAP31 induces mitochondrial fission through endoplasmic reticulum calcium signals, enhancing cytochrome c release to the cytosol

2003 ◽  
Vol 160 (7) ◽  
pp. 1115-1127 ◽  
Author(s):  
David G. Breckenridge ◽  
Marina Stojanovic ◽  
Richard C. Marcellus ◽  
Gordon C. Shore
Keyword(s):  
Endoplasmic Reticulum ◽  
Cytochrome C ◽  
Mitochondrial Fission ◽  
Integral Membrane Protein ◽  
Caspase 8 ◽  
Cytochrome C Release ◽  
Caspase Cleavage ◽  
Endoplasmic Reticulum Calcium ◽  
Induced Apoptosis ◽  
Stress Pathway

Stimulation of cell surface death receptors activates caspase-8, which targets a limited number of substrates including BAP31, an integral membrane protein of the endoplasmic reticulum (ER). Recently, we reported that a caspase-resistant BAP31 mutant inhibited several features of Fas-induced apoptosis, including the release of cytochrome c (cyt.c) from mitochondria (Nguyen, M., D.G. Breckenridge, A. Ducret, and G.C. Shore. 2000. Mol. Cell. Biol. 20:6731–6740), implicating ER-mitochondria crosstalk in this pathway. Here, we report that the p20 caspase cleavage fragment of BAP31 can direct pro-apoptotic signals between the ER and mitochondria. Adenoviral expression of p20 caused an early release of Ca2+ from the ER, concomitant uptake of Ca2+ into mitochondria, and mitochondrial recruitment of Drp1, a dynamin-related protein that mediates scission of the outer mitochondrial membrane, resulting in dramatic fragmentation and fission of the mitochondrial network. Inhibition of Drp1 or ER-mitochondrial Ca2+ signaling prevented p20-induced fission of mitochondria. p20 strongly sensitized mitochondria to caspase-8–induced cyt.c release, whereas prolonged expression of p20 on its own ultimately induced caspase activation and apoptosis through the mitochondrial apoptosome stress pathway. Therefore, caspase-8 cleavage of BAP31 at the ER stimulates Ca2+-dependent mitochondrial fission, enhancing the release of cyt.c in response to this initiator caspase.

scholarly journals Caspase cleavage of cytochrome c1 disrupts mitochondrial function and enhances cytochrome c release

Cell Research ◽  
2011 ◽  
Vol 22 (1) ◽  
pp. 127-141 ◽  
Author(s):  
Yushan Zhu ◽  
Min Li ◽  
Xiaohui Wang ◽  
Haijing Jin ◽  
Shusen Liu ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Mitochondrial Function ◽  
Cytochrome C Release ◽  
Caspase Cleavage ◽  
Cytochrome C1

scholarly journals Mitochondria-Associated Membranes (MAMs) are involved in Bax mitochondrial localization and cytochrome c release

2018 ◽  
Author(s):  
Alexandre Légiot ◽  
Claire Céré ◽  
Thibaud Dupoiron ◽  
Mohamed Kaabouni ◽  
Stéphen Manon
Keyword(s):  
Endoplasmic Reticulum ◽  
Cytochrome C ◽  
Mitochondrial Membrane ◽  
Human Protein ◽  
Outer Mitochondrial Membrane ◽  
Yeast Mutant ◽  
Mitochondrial Localization ◽  
Cytochrome C Release ◽  
Apoptotic Protein

AbstractThe distribution of the pro-apoptotic protein Bax in the outer mitochondrial membrane (OMM) is a central point of regulation of apoptosis. It is now widely recognized that parts of the endoplasmic reticulum (ER) are closely associated to the OMM, and are actively involved in different signalling processes. We adressed a possible role of these domains, called Mitochondria-Associated Membranes (MAMs) in Bax localization and fonction, by expressing the human protein in a yeast mutant deleted of MDM34, a ERMES component (ER-Mitochondria Encounter Structure). By affecting MAMs stability, the deletion of MDM34 altered Bax mitochondrial localization, and decreased its capacity to release cytochrome c. Furthermore, the deletion of MDM34 decreased the size of an uncompletely released, MAMs-associated pool of cytochrome c.

scholarly journals Drp1-dependent mitochondrial fission via MiD49/51 is essential for apoptotic cristae remodeling

2016 ◽  
Vol 212 (5) ◽  
pp. 531-544 ◽  
Author(s):  
Hidenori Otera ◽  
Non Miyata ◽  
Osamu Kuge ◽  
Katsuyoshi Mihara
Keyword(s):  
Cytochrome C ◽  
Cell Lines ◽  
Mitochondrial Fission ◽  
Intrinsic Apoptosis ◽  
Cytochrome C Release ◽  
Marked Contrast

Mitochondrial fission facilitates cytochrome c release from the intracristae space into the cytoplasm during intrinsic apoptosis, although how the mitochondrial fission factor Drp1 and its mitochondrial receptors Mff, MiD49, and MiD51 are involved in this reaction remains elusive. Here, we analyzed the functional division of these receptors with their knockout (KO) cell lines. In marked contrast to Mff-KO cells, MiD49/MiD51-KO and Drp1-KO cells completely resisted cristae remodeling and cytochrome c release during apoptosis. This phenotype in MiD49/51-KO cells, but not Drp1-KO cells, was completely abolished by treatments disrupting cristae structure such as OPA1 depletion. Unexpectedly, OPA1 oligomers generally thought to resist cytochrome c release by stabilizing the cristae structure were similarly disassembled in Drp1-KO and MiD49/51-KO cells, indicating that disassembly of OPA1 oligomers is not directly linked to cristae remodeling for cytochrome c release. Together, these results indicate that Drp1-dependent mitochondrial fission through MiD49/MiD51 regulates cristae remodeling during intrinsic apoptosis.

scholarly journals Bax- or Bak-Induced Mitochondrial Fission Can Be Uncoupled from Cytochrome c Release

2008 ◽  
Vol 31 (4) ◽  
pp. 570-585 ◽  
Author(s):  
Clare Sheridan ◽  
Petrina Delivani ◽  
Sean P. Cullen ◽  
Seamus J. Martin
Keyword(s):  
Cytochrome C ◽  
Mitochondrial Fission ◽  
Cytochrome C Release

Interleukin-11 antagonizes Fas ligand-mediated apoptosis in IEC-18 intestinal epithelial crypt cells: role of MEK and Akt-dependent signaling

2008 ◽  
Vol 294 (3) ◽  
pp. G728-G737 ◽  
Author(s):  
Kaitlin M. Naugler ◽  
Kathy A. Baer ◽  
Mark J. Ropeleski
Keyword(s):  
Cell Death ◽  
Cytochrome C ◽  
Dna Cleavage ◽  
Caspase 3 ◽  
Fas Ligand ◽  
Dependent Manner ◽  
Caspase 9 ◽  
Cytochrome C Release ◽  
Caspase Cleavage ◽  
Interleukin 11

Interleukin-11 (IL-11) displays epithelial cytoprotective effects during intestinal injury. Antiapoptotic effects of IL-11 have been described, yet mechanisms remain unclear. Fas/CD95 death receptor signaling is upregulated in ulcerative colitis, leading to mucosal breakdown. We hypothesized that IL-11 inhibits Fas ligand (FasL)-mediated apoptosis in intestinal epithelia. Cell death was monitored in IEC-18 cells by microscopy, caspase and poly(ADP-ribose) polymerase cleavage, mitochondrial release of cytochrome c, and abundance of cytoplasmic oligonucleosomal DNA. RT-PCR was used to monitor Fas, cIAP1, cIAP2, XIAP, cFLIP, survivin, and Bcl-2 family members. Fas membrane expression was detected by immunoblot. Inhibitors of JAK2, phosphatidylinositol 3-kinase (PI3-kinase), Akt 1, MEK1 and MEK2, and p38 MAPK were used to delineate IL-11's antiapoptotic mechanisms. IL-11 did not alter Fas expression. Pretreatment with IL-11 for 24 h before FasL reduced cytoplasmic oligonucleosomal DNA by 63.2%. IL-11 also attenuated caspase-3, caspase-9, and poly(ADP-ribose) polymerase cleavage without affecting expression of activated caspase-8 p20 or cytochrome c release. IL-11 did not affect mRNA expression of the candidate antiapoptotic genes. The MEK1 and MEK2 inhibitors U-0126 and PD-98059 significantly attenuated the protection of IL-11 against caspase-3 and caspase-9 cleavage and cytoplasmic oligonucleosomal DNA accumulation. Although Akt inhibition reversed IL-11-mediated effects on caspase cleavage, it did not reverse the protective effects of IL-11 by DNA ELISA. We conclude that IL-11-dependent MEK1 and MEK2 signaling inhibits FasL-induced apoptosis. The lack of reversal of the IL-11 effect on DNA cleavage by Akt inhibition, despite antagonism of caspase cleavage, suggests that IL-11 inhibits caspase-independent cell death signaling by FasL in a MEK-dependent manner.

scholarly journals The Mitochondrial Fission Protein hFis1 Requires the Endoplasmic Reticulum Gateway to Induce Apoptosis

2006 ◽  
Vol 17 (11) ◽  
pp. 4593-4605 ◽  
Author(s):  
Emilie Alirol ◽  
Dominic James ◽  
Denise Huber ◽  
Andrea Marchetto ◽  
Lodovica Vergani ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Cell Division ◽  
Cytochrome C ◽  
Mitochondrial Fission ◽  
Apoptosis Induction ◽  
Mitochondrial Fragmentation ◽  
Bifunctional Protein ◽  
Dependent Cell ◽  
Induced Fission

Mitochondrial fission ensures organelle inheritance during cell division and participates in apoptosis. The fission protein hFis1 triggers caspase-dependent cell death, by causing the release of cytochrome c from mitochondria. Here we show that mitochondrial fission induced by hFis1 is genetically distinct from apoptosis. In cells lacking the multidomain proapoptotic Bcl-2 family members Bax and Bak (DKO), hFis1 caused mitochondrial fragmentation but not organelle dysfunction and apoptosis. Similarly, a mutant in the intermembrane region of hFis1-induced fission but not cell death, further dissociating mitochondrial fragmentation from apoptosis induction. Selective correction of the endoplasmic reticulum (ER) defect of DKO cells restored killing by hFis1, indicating that death by hFis1 relies on the ER gateway of apoptosis. Consistently, hFis1 did not directly activate BAX and BAK, but induced Ca2+-dependent mitochondrial dysfunction. Thus, hFis1 is a bifunctional protein that independently regulates mitochondrial fragmentation and ER-mediated apoptosis.

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