Trans-complex formation by proteolipid channels in the terminal phase of membrane fusion

Peters, Christopher M.; Bayer, Martin; Bühler, Susanne; Andersen, Jens S.; Mann, Matthias; Mayer, Andreas

doi:10.1038/35054500

Cited by 487 publications

(513 citation statements)

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“…Alternatively, overexpression of mitofusin(s) alone may not be sufficient to increase the activity the fusion machinery, which probably involves numerous proteins. Further work is necessary to understand mitochondrial fusion and whether and how it resembles membrane fusion in other systems (Jahn and Sü dhof, 1999;Heiman and Walter, 2000;Peters et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial Fusion in Human Cells Is Efficient, Requires the Inner Membrane Potential, and Is Mediated by Mitofusins

Legros

Lombès

Frachon

et al. 2002

MBoC

585

399

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Mitochondrial fusion remains a largely unknown process despite its observation by live microscopy and the identification of few implicated proteins. Using green and red fluorescent proteins targeted to the mitochondrial matrix, we show that mitochondrial fusion in human cells is efficient and achieves complete mixing of matrix contents within 12 h. This process is maintained in the absence of a functional respiratory chain, despite disruption of microtubules or after significant reduction of cellular ATP levels. In contrast, mitochondrial fusion is completely inhibited by protonophores that dissipate the inner membrane potential. This inhibition, which results in rapid fragmentation of mitochondrial filaments, is reversible: small and punctate mitochondria fuse to reform elongated and interconnected ones upon withdrawal of protonophores. Expression of wild-type or dominant-negative dynamin-related protein 1 showed that fragmentation is due to dynamin-related protein 1-mediated mitochondrial division. On the other hand, expression of mitofusin 1 (Mfn1), one of the human Fzo homologues, increased mitochondrial length and interconnectivity. This process, but not Mfn1 targeting, was dependent on the inner membrane potential, indicating that overexpressed Mfn1 stimulates fusion. These results show that human mitochondria represent a single cellular compartment whose exchanges and interconnectivity are dynamically regulated by the balance between continuous fusion and fission reactions. INTRODUCTIONThe morphology and distribution of mitochondria differ significantly between the cells of different species and tissues. In addition, mitochondrial volume and morphology vary in function of cellular metabolism, are modulated during cell cycle and development, and during apoptosis (Stevens, 1981;Tzagoloff, 1982;Bereiter-Hahn and Voth, 1994;Church and Poyton, 1998;Diaz et al., 1999;Frank et al., 2001). Live microscopy has revealed that mitochondrial morphology is continuously remodeled by fission and fusion (Nunnari et al., 1997;Rizzuto et al., 1998). In yeast, selective inhibition of either process significantly modifies mitochondrial size and interconnectivity (Bleazard et al., 1999;Sesaki and Jensen, 1999). Among the best known proteins involved in mitochondrial dynamics are Fzo/ mitofusin, a transmembrane GTPase involved in fusion (Hales and Fuller, 1997;Hermann et al., 1998;Santel and Fuller, 2001;Rojo et al., 2002), and Dnm1p/dynamin-related protein 1 (Drp1), a dynamin-related protein involved in fission (Bleazard et al., 1999;Pitts et al., 1999;Smirnova et al., 2001).In yeast, mitochondrial fusion has been demonstrated by the diffusion and/or mixing of different matrix proteins during mating of haploid cells (Azpiroz and Butow, 1993;Nunnari et al., 1997). In contrast, mitochondrial fusion has not been studied with similar assays in human cells, and it is not known to what extent the apparent fusion events observed by live microscopy correspond to the formation of intermitochondrial junctions (Bakeeva et al., 1978;Amche...

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Section: Discussionmentioning

confidence: 99%

Mitochondrial Fusion in Human Cells Is Efficient, Requires the Inner Membrane Potential, and Is Mediated by Mitofusins

Legros

Lombès

Frachon

et al. 2002

MBoC

585

399

View full text Add to dashboard Cite

show abstract

“…On the other hand, the vesicle fusion and its apparatus must be more or less similar among different types of neurons [63][64][65][66][67]. In any case, however, the evidence for somatic or dendritic release of DA through ATP6V0C in non-dopaminergic neurons or glia is likely to be very weak at this moment.…”

Section: Overview Of Gene or Cell Transplantation Therapy For Neurodementioning

confidence: 99%

“…It is possible to postulate another mechanism whereby a complex of proteolipid channels involved in SNARE fusion may effectively secrete DA from DA-accumulating cells in the striatum, as described in yeast and Drosophila [7,65,66].…”

Section: Overview Of Gene or Cell Transplantation Therapy For Neurodementioning

confidence: 99%

Neurotransmitter release: vacuolar ATPase V0 sector c-subunits in possible gene or cell therapies for Parkinson’s, Alzheimer’s, and psychiatric diseases

et al. 2016

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Gene therapy or cell transplantation therapy has made great progress in recent years. We overview mediatophore as a potential medical usage for gene and transplantation therapies in the nervous system. The 16-kDa proteolipid mediatophore was shown to mediate the secretion of acetylcholine in a Ca 2+ -dependent manner. Mediatophore is known to be identical to the transmembrane c-subunit of the V0 sector of the vacuolar proton ATPase (ATP6V0C).Recent development of structural understandings reveals that ATP6V0C is not a simple pore-forming stalk enable to permeate transmitters.Therefore, it is time to review this topic revisited from the recent knowledge on ATPase.

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“…Also, transfection of neuroblastoma N18-TG-2 cells with mediatophore cDNA induced both a Ca 2þ -dependent and quantal ACh release (Falk-Vairant et al, 1996a;, and a transient increase of medium and large IMPs , as summarised in Table 1. The 15-kDa proteolipid forming mediatophore is implicated in several cellular processes. It is a component of the membrane sector of V-ATPase (Nelson and Harvey, 1999); it was found in invertebrate gap junctions (Finbow and Pitts, 1998) and was recently identi¢ed in the yeast as the Ca 2þ -sensitive proteolipid involved in membrane fusion (Peters et al, 2001). As suggested by the latter authors, it is possible that the proteolipid rings of 15-kDa subunits forming mediatophores expand radially during opening.…”

Section: Signi¢cance Of the Imp Changesmentioning

confidence: 96%

Quantal transmitter release by glioma cells: quantification of intramembrane particle changes

Bugnard¹,

Taulier²,

Bloc³

et al. 2002

Neuroscience

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AbstractöGlial cells in situ are able to release neurotransmitters such as glutamate or acetylcholine (ACh). Glioma C6BU-1 cells were used to determine whether the mechanisms of ACh release by a glial cell line are similar or not to quantal release from neurones. Individual C6BU-1 cells, pre-¢lled with ACh, were moved into contact with a Xenopus myocyte that was used as a real-time ACh detector. Upon electrical stimulation, C6BU-1 cells generated evoked ACh impulses which were Ca 2þ -dependent and quantal (quantal steps of ca. 100 pA). Changes in plasma membrane ultrastructure were investigated by using a freeze-fracture technique designed for obtaining large and £at replicas from monolayer cell cultures. A transient increase in the density of medium and large size intramembrane particles^and a corresponding decrease of small particles^occurred in the plasma membrane of C6BU-1 cells stimulated for ACh release. Changes in interaction forces between adjacent medium and large particles were investigated by computing the radial distribution function and the interaction potential. In resting cells, the radial distribution function revealed a signi¢cant increase in the probability to ¢nd two particles separated by an interval of 24 nm; the interaction potential suggested repulsive forces for intervals shorter than 24 nm and attractive forces between 24 and 26 nm. In stimulated cells, this interaction was displaced to 21 nm and made weaker, despite of the fact that the overall particle density increased. The nature of this transient change in intramembrane particles is discussed, particularly with regard to the mediatophore proteolipid which is abundant in the membranes C6-BU-1 like in those of cholinergic neurones. In conclusion, evoked ACh release from pre-¢lled C6-BU-1 glioma cells is quantal and Ca 2þ -dependent. It is accompanied by a transient changes in the size distribution and the organisation of intramembrane particles in the plasma membrane. Thus, for the release characteristics, glioma cells do not di¡er fundamentally from neurones. ß

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Trans-complex formation by proteolipid channels in the terminal phase of membrane fusion

Cited by 487 publications

References 50 publications

Mitochondrial Fusion in Human Cells Is Efficient, Requires the Inner Membrane Potential, and Is Mediated by Mitofusins

Mitochondrial Fusion in Human Cells Is Efficient, Requires the Inner Membrane Potential, and Is Mediated by Mitofusins

Neurotransmitter release: vacuolar ATPase V0 sector c-subunits in possible gene or cell therapies for Parkinson’s, Alzheimer’s, and psychiatric diseases

Quantal transmitter release by glioma cells: quantification of intramembrane particle changes

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