Mitochondria-Derived and Extra-Mitochondrial Human Type-1 Porin Are Identical as Revealed by Amino Acid Sequencing and Electrophysiological Characterisation

Stadtmüller, Ulrike; Eben-Brunnen, Jana; Schmid, Alex P.; Hesse, Dörte; Klebert, Simone; Kratzin, Hartmut; Hesse, Jan; Zimmermann, Bodo; Reymann, Susanne; Thinnes, Friedrich P.; Benz, Roland; Götz, H.; Hilschmann, Norbert

doi:10.1515/bc.1999.189

Cited by 10 publications

(4 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We postulate that VDAC1 overexpression leads to its targeting to extra-mitochondrial locations. Plasma membrane resident VDAC1 has been documented in various mouse and human tissues with the mitochondrial surface residues facing the extracellular space ( Akanda et al., 2008 , Buettner et al., 2000 , De Pinto et al., 2010 , Okada et al., 2004 , Stadtmuller et al., 1999 , Thinnes, 2015 ). In neurons, plVDAC1 activation initiated apoptosis, prevented by antibodies directed against the extracellular N terminus of VDAC1 ( Akanda et al., 2008 , Smilansky et al., 2015 ).…”

Section: Resultsmentioning

confidence: 99%

“…The impaired metabolism-secretion coupling prompted us to examine the cellular localization of VDAC1 and VDAC2. Extra-mitochondrial plasma membrane VDAC1 (De Pinto et al., 2010, Stadtmuller et al., 1999, Thinnes, 2015) participates in volume regulation, ATP and metabolite transport, and intrinsic mitochondrial apoptosis (Akanda et al., 2008, Okada et al., 2004, Shoshan-Barmatz et al., 2010). Remarkably, confocal microscopy reveals that VDAC1, but not VDAC2, surface expression occurs in β cells from T2D donors (Figures 4A and 4B).…”

Section: Resultsmentioning

confidence: 99%

“…As mtVDAC1 and pl-VDAC1 display identical amino acid sequences (Shoshan-Barmatz et al., 2010, Stadtmuller et al., 1999), we next performed channel conductance recordings with purified mitochondrial VDAC1 protein reconstituted into planar lipid bilayers (Ben-Hail et al., 2016). Metformin (30 μM) decreases channel conductance to a low conducting state imposed (Figures 5E, S5E, and S5F) like the specific VDAC inhibitor VBIT-4 (Figures 5F, S5G, and S5H).…”

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

Preserving Insulin Secretion in Diabetes by Inhibiting VDAC1 Overexpression and Surface Translocation in β Cells

et al. 2019

View full text Add to dashboard Cite

SummaryType 2 diabetes (T2D) develops after years of prediabetes during which high glucose (glucotoxicity) impairs insulin secretion. We report that the ATP-conducting mitochondrial outer membrane voltage-dependent anion channel-1 (VDAC1) is upregulated in islets from T2D and non-diabetic organ donors under glucotoxic conditions. This is caused by a glucotoxicity-induced transcriptional program, triggered during years of prediabetes with suboptimal blood glucose control. Metformin counteracts VDAC1 induction. VDAC1 overexpression causes its mistargeting to the plasma membrane of the insulin-secreting β cells with loss of the crucial metabolic coupling factor ATP. VDAC1 antibodies and inhibitors prevent ATP loss. Through direct inhibition of VDAC1 conductance, metformin, like specific VDAC1 inhibitors and antibodies, restores the impaired generation of ATP and glucose-stimulated insulin secretion in T2D islets. Treatment of db/db mice with VDAC1 inhibitor prevents hyperglycemia, and maintains normal glucose tolerance and physiological regulation of insulin secretion. Thus, β cell function is preserved by targeting the novel diabetes executer protein VDAC1.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Preserving Insulin Secretion in Diabetes by Inhibiting VDAC1 Overexpression and Surface Translocation in β Cells

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Antibodies raised against the N-terminus of VDAC1 interacted with the plasma membrane of bovine astrocytes and blocked a high conductance anion channel [61]. Interestingly, when detected in the plasma membrane (pl-VDAC1), the amino acid residues that were exposed to the cytosol in the mitochondrial protein were found to face the extracellular space [55,60,[68][69][70][71]. This was demonstrated in epithelial cells, astrocytes, and neurons [56,57] and in differentiated hippocampal neurons [55].…”

mentioning

confidence: 97%

VDAC1 at the Intersection of Cell Metabolism, Apoptosis, and Diseases

2020

View full text Add to dashboard Cite

The voltage-dependent anion channel 1 (VDAC1) protein, is an important regulator of mitochondrial function, and serves as a mitochondrial gatekeeper, with responsibility for cellular fate. In addition to control over energy sources and metabolism, the protein also regulates epigenomic elements and apoptosis via mediating the release of apoptotic proteins from the mitochondria. Apoptotic and pathological conditions, as well as certain viruses, induce cell death by inducing VDAC1 overexpression leading to oligomerization, and the formation of a large channel within the VDAC1 homo-oligomer. This then permits the release of pro-apoptotic proteins from the mitochondria and subsequent apoptosis. Mitochondrial DNA can also be released through this channel, which triggers type-Ι interferon responses. VDAC1 also participates in endoplasmic reticulum (ER)-mitochondria cross-talk, and in the regulation of autophagy, and inflammation. Its location in the outer mitochondrial membrane, makes VDAC1 ideally placed to interact with over 100 proteins, and to orchestrate the interaction of mitochondrial and cellular activities through a number of signaling pathways. Here, we provide insights into the multiple functions of VDAC1 and describe its involvement in several diseases, which demonstrate the potential of this protein as a druggable target in a wide variety of pathologies, including cancer.

show abstract

Expanding the protein catalogue in the proteome reference map of human breast cancer cells

Pucci‐Minafra

Cancemi²,

Fontana³

et al. 2006

Proteomics

View full text Add to dashboard Cite

In this report we present a catalogue of 162 proteins (including isoforms and variants) identified in a prototype of proteomic map of breast cancer cells. This work represents the prosecution of previous studies describing the protein complement of breast cancer cells of the line 8701-BC, which has been well characterized for several parameters, providing to be a useful model for the study of breast cancer-associated candidate biomarkers. In particular, 110 spots were identified ex novo by PMF, or validated following previous gel matching identification method; 30 were identified by N-terminal microsequencing and the remaining by gel matching with maps available from our former work. As a consequence of the expanded number of proteins, we have updated our previous classification extending the number of protein groups from 4 to 13. In order to facilitate comparative proteome studies of different kinds of breast cancers, in this report we provide the whole complement of proteins so far identified and grouped into the new classification. A consistent number of them were not described before in other proteomic maps of breast cancer cells or tissues, and therefore they represent a valuable contribution for breast cancer protein databases and for future application in basic and clinical researches.

show abstract

Mitochondria-Derived and Extra-Mitochondrial Human Type-1 Porin Are Identical as Revealed by Amino Acid Sequencing and Electrophysiological Characterisation

Cited by 10 publications

References 22 publications

Preserving Insulin Secretion in Diabetes by Inhibiting VDAC1 Overexpression and Surface Translocation in β Cells

Preserving Insulin Secretion in Diabetes by Inhibiting VDAC1 Overexpression and Surface Translocation in β Cells

VDAC1 at the Intersection of Cell Metabolism, Apoptosis, and Diseases

Expanding the protein catalogue in the proteome reference map of human breast cancer cells

Contact Info

Product

Resources

About