Bid-induced Cytochrome c Release Is Mediated by a Pathway Independent of Mitochondrial Permeability Transition Pore and Bax

Kim, Tae Hyoung; Zhao, Yongge; Barber, Michael J.; Kuharsky, Diane K.; Yin, Xiao‐Ming

doi:10.1074/jbc.m003370200

Cited by 171 publications

(174 citation statements)

References 53 publications

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“…Furthermore, due to the unavailability of commercial antibodies, we could not distinguish between full length and truncated Bid. However, as previously mentioned, both forms possess apoptogenic properties (Kim, Zhao, Barber, Kuharsky, and Yin 2000;Konig, Rehm, Gudorf, Krajewski, Gross, Ward, and Prehn 2007). Therefore, an increased mitochondrial content of Bid, regardless of its cleavage, may still be considered as part of the pro-apoptotic environment taking place in aged skeletal muscle.…”

Section: Discussionmentioning

confidence: 85%

“…While this finding may be interpreted as a compensatory action aimed at preventing myonuclei loss, we found a concomitant increase of total mitochondrial content of Bid. Recent experimental evidence indicates that full length Bid and tBid are sufficient to elicit mitochondrial cell death pathways (Kim et al 2000;Konig et al 2007). In an elegant experiment, Scorrano and coworkers (Scorrano et al 2002), demonstrated that tBid induced a dose-dependent release of cytochrome c from isolated mitochondria.…”

Section: Discussionmentioning

confidence: 99%

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Age-related activation of mitochondrial caspase-independent apoptotic signaling in rat gastrocnemius muscle

Marzetti

Wohlgemuth

Lees

et al. 2008

Mechanisms of Ageing and Development

156

149

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Mitochondria-mediated apoptosis represents a central process driving age-related muscle loss. However, the temporal relation between mitochondrial apoptotic signaling and sarcopenia as well as the regulation of release of pro-apoptotic factors from the mitochondria has not been elucidated. In this study, we investigated mitochondrial apoptotic signaling in skeletal muscle of rats across a wide age range. We also investigated whether mitochondrial-driven apoptosis was accompanied by changes in the expression of Bcl-2 proteins and components of the mitochondrial permeability transition pore (mPTP). Analyses were performed on gastrocnemius muscle of 8-, 18-, 29-and 37-month-old male Fischer 344 ×Brown Norway rats (9 per group). Muscle weight declined progressively with advancing age, concomitant with increased apoptotic DNA fragmentation. Cytosolic and nuclear levels of apoptosis inducing factor (AIF) and endonuclease G (EndoG) increased in old and senescent animals. In contrast, cytosolic levels of cytochrome c were unchanged with age. Mitochondrial Bcl-2, Bax and Bid increased dramatically in 37-month-old rats, with no changes in the Bax/Bcl-2 ratio in any of the age groups. Finally, expression of cyclophilin D was enhanced at very old age. Our findings indicate that the mitochondrial caspase-independent apoptotic pathway may play a more prominent role in skeletal muscle loss than caspase-mediated apoptosis.

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Section: Discussionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Age-related activation of mitochondrial caspase-independent apoptotic signaling in rat gastrocnemius muscle

Marzetti

Wohlgemuth

Lees

et al. 2008

Mechanisms of Ageing and Development

156

149

View full text Add to dashboard Cite

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“…TRAIL treatment induced the loss of full-length Bid consistent with caspase-8-dependent Bid cleavage (13). Translocation of Bid to the mitochondria has been shown to engage the intrinsic apoptotic pathway after a death receptor stimulus such as TRAIL (12,14). Furthermore, the TRAILinduced cleavage of DFF45, a substrate of caspase-3, was completely blocked in SW480/Bcl-2 cells in contrast to SW480/neo cells (Fig.…”

Section: Bcl-2 Overexpression Protects Against Trail-inducedmentioning

confidence: 83%

“…1 Schematic diagram of the death receptor-mediated "extrinsic" and mitochondrial or "intrinsic" apoptotic pathways. Signals originating from membrane death receptors may cross-talk with the mitochondria by caspase-8-mediated cleavage of the proapoptotic Bcl-2 family member, Bid (12)(13)(14). Bid is then translocated to mitochondria where it can trigger cytochrome c release.…”

Section: Methodsmentioning

confidence: 99%

Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand–Induced Apoptosis Is Inhibited by Bcl-2 but Restored by the Small Molecule Bcl-2 Inhibitor, HA 14-1, in Human Colon Cancer Cells

Sinicrope

Penington

Tang

2004

Clinical Cancer Research

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Purpose: Tumor necrosis factor-related apoptosisinducing ligand (TRAIL) is a promising anticancer agent that induces apoptosis in multiple tumor cell types while sparing most normal cells. We determined the effect of ectopic Bcl-2 expression on TRAIL-induced apoptosis and whether the small molecule Bcl-2 inhibitor, HA14-1, could increase TRAIL sensitivity. Conclusions: Bcl-2 confers apoptosis resistance to TRAIL by inhibiting a mitochondrial amplification step and by inactivating downstream XIAP in SW480 cells. HA14-1 reversed Bcl-2-mediated TRAIL resistance, suggesting a novel strategy for increasing TRAIL sensitivity in Bcl-2-overexpressing colon cancers.

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“…Also, in ANT-deficient hepatocytes no altered apoptosis responses to the ligands of the Fas-and the TNF-receptor were observed. However, it is contentious [109,110] whether the PT-pore in mitochondria is activated by these cell death signals that act at the plasma membrane and hence whether an altered apoptosis (and necrosis) response could have been expected. Furthermore, since this study was published another isoform of ANT (ANT4) has been discovered in the mouse genome [111].…”

Section: Ant Knock-out Studiesmentioning

confidence: 99%

The permeability transition pore in cell death

2007

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The permeability transition pore (PT-pore) is a multi-component protein aggregate in mitochondria that comprises factors in the inner as well as in the outer mitochondrial membrane. This complex has two functions: firstly, it regulates the integration of oxidative phosphorylation into the cellular energy household and secondly, it induces cell death when converted into an unspecific channel. The latter causes a collapse of the mitochondrial membrane potential and activates a chain of events that culminate in the demise of the cell. It has been controversial for some time whether the PT-pore is causative for or only amplifies a signal of cell death but novel results confirm a central role of this protein complex for cell death induction. While a considerable body of data exist on its subunit composition, recent genetic knock-out experiments suggest that the identity of the core factors of the PT-pore is still unresolved. Moreover, accumulating evidence point to a much more complex composition of this protein complex than anticipated. Here, we review the current knowledge of its subunit composition, the evidence of a role in cell death, and we propose a model for the activation of the PT-pore for cell death. The role of the PT-pore in apoptosisThe permeability transitionThe permeability transition (PT) is a sudden and sustained increase of the permeability of the inner mitochondrial membrane for solutes smaller than 1.5 kD. This has catastrophic consequences for this organelle. The mitochondrial membrane potential m , which relies on the im-permeability of the inner membrane for protons, breaks down and with it the ability of the cell to synthesize ATP. The ensuing blockade of the respiratory chain leads to the generation of reactive oxygen intermediates (ROIs), most likely via the direct transfer of electrons to molecular oxygen. Also, the high concentration of solutes in the mitochondrial matrix generates an osmotic pressure, which drives the influx of water molecules and the expansion of the extensively folded inner membrane and eventually disrupts the outer membrane leading to the release of factors that execute the suicide programme of apoptosis. Thus, the self-destruction of mitochondria via the PT is followed by the demise of the cell as a whole. This process of mitochondrial destruction was first observed in vitro but was dismissed at the time as an artefact because, among other reasons, it was inconceivable why mitochondria should dispose of a process to dismantle themselves. This changed, however, when it was shown that the PT is mediated by a protein complex, the so-called permeability transition pore (PT-pore), and that various physiological and pharmacological reagents can act on this pore and modify the deadly response of mitochondria. Finally, the realisation that cells can mount an active suicide response that is mediated in large part by mitochondria placed the PT-pore firmly on the map of researchers. In particular, the use of cyclosporine A (CsA) that can inhibit the PT-pore subunit cyc...

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Bid-induced Cytochrome c Release Is Mediated by a Pathway Independent of Mitochondrial Permeability Transition Pore and Bax

Cited by 171 publications

References 53 publications

Age-related activation of mitochondrial caspase-independent apoptotic signaling in rat gastrocnemius muscle

Age-related activation of mitochondrial caspase-independent apoptotic signaling in rat gastrocnemius muscle

Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand–Induced Apoptosis Is Inhibited by Bcl-2 but Restored by the Small Molecule Bcl-2 Inhibitor, HA 14-1, in Human Colon Cancer Cells

The permeability transition pore in cell death

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