Intersection between Mitochondrial Permeability Pores and Mitochondrial Fusion/Fission

Gazaryan, I. G.; Brown, Abraham M.

doi:10.1007/s11064-006-9252-2

Cited by 34 publications

(20 citation statements)

References 116 publications

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“…It is not clear if the MPT pore itself is directly associated with Bax, Bak or other Bcl-2 family proteins, but MPT pore activity can be influenced by Bcl-2 proteins. It is to be emphasized that while earlier work was interpreted to indicate that the MPT pore and the OMM pore opened in concert with one another, it is now known that each is subject to its own regulation and can function independently of the other (18,19). The MPT apparatus may nonetheless be important in facilitating mitochondrial protein redistribution from the IMS, as its opening causes swelling of mitochondria as outlined below.…”

Section: Mitochondrial Changes At the Ultrastructural Levelmentioning

confidence: 97%

The mitochondrial gateway to cell death

Smith

Kluck

et al. 2008

IUBMB Life

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Mitochondria play a key role in death signaling. The intermembrane space of these organelles contains a number of proteins which promote cell death once they are redistributed to the cytosol. The formation of pores in the outer membrane of mitochondria defines a gateway through which the apoptogenic proteins pass during death signaling. Interactions between pro‐apoptotic and pro‐survival members of the Bcl‐2 family of proteins are decisive in the initiation of pore opening. While the specific composition of the pore in molecular terms is still subject to debate and continuing investigation, it is recognized functionally as a passive channel which not only allows egress of proteins to cytosol but also entry in the reverse direction. A variety of constraints may restrict the release of proteins from the intermembrane space to the cytosol. These include trapping in the intercristal spaces formed by the convoluted invaginations of the inner membrane, binding of proteins to the inner membrane or to other soluble proteins of the intermembrane space, or insertion of proteins into the inner membrane. There is a corresponding variety of mechanisms that facilitate release of apoptogenic proteins from such entrapment. Morphological changes that expand the inner membrane enable proteins to be released from enclosure in intercristal spaces, allowing these proteins access to the mitochondrial gateway. Specific cases include cytochrome c molecules bound to inner membrane cardiolipin and released upon oxidation of that lipid component. Further, AIF that is embedded in the inner membrane is released by proteases (caspases or calpains), which enter from the cytosol once the outer membrane pore has opened. The facilitation (or restriction) of apoptogenic protein release through the mitochondrial gateway may provide new opportunities for regulating cell death. © 2008 IUBMB IUBMB Life, 60(6): 383–389, 2008.

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Section: Mitochondrial Changes At the Ultrastructural Levelmentioning

confidence: 97%

The mitochondrial gateway to cell death

Smith

Kluck

et al. 2008

IUBMB Life

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“…Bcl-2 is the master anti-apoptotic member of the family, and prevents apoptosis by maintaining mitochondrial membrane integrity [3,16,24,25]. Bcl-2 inhibits apoptosis by heterodimerization with Bad/Bax apoptotic members and preventing their clustering into pores, or sequestering Bim apoptotic activators [21,26].…”

Section: Intrinsic Pathwaymentioning

confidence: 99%

Anoikis: an emerging hallmark in health and diseases

Taddei

Giannoni

Fiaschi

et al. 2011

The Journal of Pathology

528

404

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Anoikis is a programmed cell death occurring upon cell detachment from the correct extracellular matrix, thus disrupting integrin ligation. It is a critical mechanism in preventing dysplastic cell growth or attachment to an inappropriate matrix. Anoikis prevents detached epithelial cells from colonizing elsewhere and is thus essential for tissue homeostasis and development. As anchorage-independent growth and epithelial-mesenchymal transition, two features associated with anoikis resistance, are crucial steps during tumour progression and metastatic spreading of cancer cells, anoikis deregulation has now evoked particular attention from the scientific community. The aim of this review is to analyse the molecular mechanisms governing both anoikis and anoikis resistance, focusing on their regulation in physiological processes, as well as in several diseases, including metastatic cancers, cardiovascular diseases and diabetes.

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“…9 The process of mitochondrial inner membrane permeabilization (MIMP) is often associated with permeability transition pore (PTP) opening. [10][11][12][13] The PTP is a multi-protein complex which as yet is poorly defined at the molecular level. Previously the PTP was thought to comprise the adenosine nucleotide translocator and cyclophilin D on the IMM complexed with voltage dependent anion channel and the peripheral benzodiazepine receptor on the OMM.…”

mentioning

confidence: 99%

A novel paradigm for rapid ABT-737-induced apoptosis involving outer mitochondrial membrane rupture in primary leukemia and lymphoma cells

et al. 2008

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Primary chronic lymphocytic leukemia (CLL) cells are exquisitely sensitive to ABT-737, a small molecule BCL2-antagonist, which induces many of the classical biochemical and ultrastructural features of apoptosis, including BAX/BAK oligomerization, cytochrome c release, caspase activation and chromatin condensation. Surprisingly, ABT-737 also induces mitochondrial inner membrane permeabilization (MIMP) resulting in mitochondrial matrix swelling and rupture of the outer mitochondrial membrane (OMM), so permitting the rapid efflux of cytochrome c from mitochondrial cristae and facilitating rapid caspase activation and apoptosis. BAX and BAK appear to be involved in the OMM discontinuities as they localize to the OMM break points. Notably, ABT-737 induced mitochondrial matrix swelling and OMM discontinuities in other primary B-cell malignancies, including mantle cell, follicular and marginal zone lymphoma cells but not in several cell lines studied. Thus, we describe a new paradigm of apoptosis in primary B-cell malignancies, whereby targeting of BCL2 results in all the classical features of apoptosis together with OMM rupture independent of caspase activation. This mechanism may be far more prevalent than hitherto recognized due to the failure of most methods, used to measure apoptosis, to recognize such a mechanism.

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Intersection between Mitochondrial Permeability Pores and Mitochondrial Fusion/Fission

Cited by 34 publications

References 116 publications

The mitochondrial gateway to cell death

The mitochondrial gateway to cell death

Anoikis: an emerging hallmark in health and diseases

A novel paradigm for rapid ABT-737-induced apoptosis involving outer mitochondrial membrane rupture in primary leukemia and lymphoma cells

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