Molecular basis of morphological changes in mitochondrial membrane accompanying induction of permeability transition, as revealed by immuno-electron microscopy

Terauchi, Satsuki; Yamamoto, Toshiharu; Yamashita, Kikuji; Kataoka, Masatoshi; Terada, Hiroshi; Shinohara, Yasuo

doi:10.1016/j.mito.2005.04.002

Cited by 9 publications

(10 citation statements)

References 16 publications

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“…In selected cases, OM permeabilization has been detected by electron microscopy, by the visualization of gaps in OM, through which IM herniation may occur (762,785). Osmotic matrix swelling due to the influx of water may culminate in OM rupture.…”

Section: A Signs Of Outer Mitochondrial Permeabilizationmentioning

confidence: 99%

“…Obviously, this mode of OM permeabilization is irreversible and so are the associated mitochondrial dysfunction and release of apoptogenic factors. Indeed, according to immunoelectron microscopy determinations, upon physical rupture of the OM following PT induction, VDAC and the subunit F1 of ATPase remain associated with mitochondrial membranes, while Cyt c staining is lost (762). Nonetheless, there is no consensus on the contribution of OM ruptures to OM permeabilization.…”

Section: A Signs Of Outer Mitochondrial Permeabilizationmentioning

confidence: 99%

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Mitochondrial Membrane Permeabilization in Cell Death

Kroemer¹,

Galluzzi²,

Brenner³

2007

Physiological Reviews

3,189

2,742

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Irrespective of the morphological features of end-stage cell death (that may be apoptotic, necrotic, autophagic, or mitotic), mitochondrial membrane permeabilization (MMP) is frequently the decisive event that delimits the frontier between survival and death. Thus mitochondrial membranes constitute the battleground on which opposing signals combat to seal the cell's fate. Local players that determine the propensity to MMP include the pro- and antiapoptotic members of the Bcl-2 family, proteins from the mitochondrialpermeability transition pore complex, as well as a plethora of interacting partners including mitochondrial lipids. Intermediate metabolites, redox processes, sphingolipids, ion gradients, transcription factors, as well as kinases and phosphatases link lethal and vital signals emanating from distinct subcellular compartments to mitochondria. Thus mitochondria integrate a variety of proapoptotic signals. Once MMP has been induced, it causes the release of catabolic hydrolases and activators of such enzymes (including those of caspases) from mitochondria. These catabolic enzymes as well as the cessation of the bioenergetic and redox functions of mitochondria finally lead to cell death, meaning that mitochondria coordinate the late stage of cellular demise. Pathological cell death induced by ischemia/reperfusion, intoxication with xenobiotics, neurodegenerative diseases, or viral infection also relies on MMP as a critical event. The inhibition of MMP constitutes an important strategy for the pharmaceutical prevention of unwarranted cell death. Conversely, induction of MMP in tumor cells constitutes the goal of anticancer chemotherapy.

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Section: A Signs Of Outer Mitochondrial Permeabilizationmentioning

confidence: 99%

Section: A Signs Of Outer Mitochondrial Permeabilizationmentioning

confidence: 99%

Mitochondrial Membrane Permeabilization in Cell Death

Kroemer¹,

Galluzzi²,

Brenner³

2007

Physiological Reviews

3,189

2,742

View full text Add to dashboard Cite

show abstract

“…Obviously, gaps in OM induced by the osmotic swelling of the matrix are associated with an irreversible permeabilization, permanent mitochondrial dysfunction and release of IMS proteins. Accordingly, Cyt c immuno-electron staining is lost in mitochondria with ruptured OM, whereas VDAC and the F1 subunit of ATPase remain associated with mitochondrial membranes [72]. Despite the large amount of additional information provided by electron microscopy, ultrastructural approaches are characterized by the following drawbacks: (1) they are laborious, and allow the analysis of a very limited number of samples; (2) they are not quantitative, because (unless hundreds of images are taken) they focus on few mitochondria of few cells; (3) they may fail to detect (unless IMS proteins are stained for immuno-electron determinations) the situations in which OM permeabilization has occurred through transient discontinuities or through the formation of supramolecular openings (e.g.…”

Section: Detection Of Om Permeabilizationmentioning

confidence: 98%

“…In this context, OM permeabilization has been visualized by means of ruptures in OM, through which IM herniation may occur [71,72]. Obviously, gaps in OM induced by the osmotic swelling of the matrix are associated with an irreversible permeabilization, permanent mitochondrial dysfunction and release of IMS proteins.…”

Section: Detection Of Om Permeabilizationmentioning

confidence: 99%

Methods for the assessment of mitochondrial membrane permeabilization in apoptosis

et al. 2007

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Mitochondrial membrane permeabilization (MMP) is considered as the "point-of-no-return" in numerous models of programmed cell death. Indeed, mitochondria determine the intrinsic pathway of apoptosis, and play a major role in the extrinsic route as well. MMP affects the inner and outer mitochondrial membranes (IM and OM, respectively) to a variable degree. OM permeabilization culminates in the release of proteins that normally are confined in the mitochondrial intermembrane space (IMS), including caspase activators (e.g. cytochrome c) and caspase-independent death effectors (e.g. apoptosis-inducing factor). Partial IM permeabilization disrupts mitochondrial ion and volume homeostasis and dissipates the mitochondrial transmembrane potential ( m ). The assessment of early mitochondrial alterations allows for the identification of cells that are committed to die but have not displayed yet the apoptotic phenotype. Several

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“…Preparation of Antisera Against Cyt c, AK2, and F 1 β and Their Affinity Purification Antibodies against three mitochondrial proteins, Cyt c, AK2, and β-subunit of F 1 -ATPase (F 1 β) were raised by injecting synthetic peptides with amino acid sequences of HTVEKGGKHKTGPNLHGLFC, TVKQAEMLDDLMDKRKEKLDC, and VPADDLTDP APATTFAHLDATTC, respectively, into New Zealand white rabbits, as described previously [12][13][14].…”

Section: Methodsmentioning

confidence: 99%

Use of Highly Purified and Mixed Antibodies for Simultaneous Detection of Multiple Protein Species Released from Mitochondria upon Induction of the Permeability Transition

Yamamoto

Ohashi

Mizutani

et al. 2010

Appl Biochem Biotechnol

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Concomitant with the induction of the mitochondrial permeability transition (PT), cytochrome c is released from mitochondria into the cytosol where it triggers subsequent steps of cellular apoptosis. Thus, inducers of the mitochondrial PT would become "seed compounds" of regulators of apoptosis. However, when we examine the actions of certain chemicals on the release of mitochondrial cytochrome c, the behaviors of not only cytochrome c but also multiple mitochondrial protein species must be carefully examined because the mitochondrial PT and release of proteins from mitochondria occur in diverse manners. In the present study, we examined whether it is possible to measure the behaviors of multiple protein species in a single experiment using purified and mixed antibodies. The results obtained clearly indicate that this procedure would be applicable for high-throughput screening of regulators of apoptosis. Further requirements necessary for the establishment of a useful screening system for apoptosis regulators are discussed.

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Molecular basis of morphological changes in mitochondrial membrane accompanying induction of permeability transition, as revealed by immuno-electron microscopy

Cited by 9 publications

References 16 publications

Mitochondrial Membrane Permeabilization in Cell Death

Mitochondrial Membrane Permeabilization in Cell Death

Methods for the assessment of mitochondrial membrane permeabilization in apoptosis

Use of Highly Purified and Mixed Antibodies for Simultaneous Detection of Multiple Protein Species Released from Mitochondria upon Induction of the Permeability Transition

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