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Prohibitin-2 Depletion Unravels Extra-Mitochondrial Functions at the Kidney Filtration Barrier

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Prohibitin-2 Depletion Unravels Extra-Mitochondrial Functions at the Kidney Filtration Barrier. / Ising, Christina; Bharill, Puneet; Brinkkoetter, Sibylle; Brähler, Sebastian; Schroeter, Christina; Koehler, Sybille; Hagmann, Henning; Merkwirth, Carsten; Höhne, Martin; Müller, Roman U; Fabretti, Francesca; Schermer, Bernhard; Bloch, Wilhelm; Kerjaschki, Dontscho; Kurschat, Christine E; Benzing, Thomas; Brinkkoetter, Paul T.

in: AM J PATHOL, Jahrgang 186, Nr. 5, 05.2016, S. 1128-39.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Ising, C, Bharill, P, Brinkkoetter, S, Brähler, S, Schroeter, C, Koehler, S, Hagmann, H, Merkwirth, C, Höhne, M, Müller, RU, Fabretti, F, Schermer, B, Bloch, W, Kerjaschki, D, Kurschat, CE, Benzing, T & Brinkkoetter, PT 2016, 'Prohibitin-2 Depletion Unravels Extra-Mitochondrial Functions at the Kidney Filtration Barrier', AM J PATHOL, Jg. 186, Nr. 5, S. 1128-39. https://doi.org/10.1016/j.ajpath.2015.12.018

APA

Ising, C., Bharill, P., Brinkkoetter, S., Brähler, S., Schroeter, C., Koehler, S., Hagmann, H., Merkwirth, C., Höhne, M., Müller, R. U., Fabretti, F., Schermer, B., Bloch, W., Kerjaschki, D., Kurschat, C. E., Benzing, T., & Brinkkoetter, P. T. (2016). Prohibitin-2 Depletion Unravels Extra-Mitochondrial Functions at the Kidney Filtration Barrier. AM J PATHOL, 186(5), 1128-39. https://doi.org/10.1016/j.ajpath.2015.12.018

Vancouver

Ising C, Bharill P, Brinkkoetter S, Brähler S, Schroeter C, Koehler S et al. Prohibitin-2 Depletion Unravels Extra-Mitochondrial Functions at the Kidney Filtration Barrier. AM J PATHOL. 2016 Mai;186(5):1128-39. https://doi.org/10.1016/j.ajpath.2015.12.018

Bibtex

@article{8ecaf988372a4831ba44daa0345c5cc0,
title = "Prohibitin-2 Depletion Unravels Extra-Mitochondrial Functions at the Kidney Filtration Barrier",
abstract = "Mitochondrial fusion is essential for maintenance of mitochondrial function and requires the prohibitin ring complex subunit prohibitin-2 (PHB2) at the mitochondrial inner membrane. Loss of the stomatin/PHB/flotillin/HflK/C (SPFH) domain containing protein PHB2 causes mitochondrial dysfunction and defective mitochondria-mediated signaling, which is implicated in a variety of human diseases, including progressive renal disease. Here, we provide evidence of additional, extra-mitochondrial functions of this membrane-anchored protein. Immunofluorescence and immunogold labeling detected PHB2 at mitochondrial membranes and at the slit diaphragm, a specialized cell junction at the filtration slit of glomerular podocytes. PHB2 coprecipitated with podocin, another SPFH domain-containing protein, essential for the assembly of the slit diaphragm protein-lipid supercomplex. Consistent with an evolutionarily conserved extra-mitochondrial function, the ortholog of PHB2 in Caenorhabditis elegans was also not restricted to mitochondria but colocalized with the mechanosensory complex that requires the podocin ortholog MEC2 for assembly. Knockdown of phb-2 partially phenocopied loss of mec-2 in touch neurons of the nematode, resulting in impaired gentle touch sensitivity. Collectively, these data indicate that, besides its established role in mitochondria, PHB2 may have an additional function in conserved protein-lipid complexes at the plasma membrane.",
keywords = "Animals, Caenorhabditis elegans Proteins, Cells, Cultured, HEK293 Cells, Humans, Intercellular Junctions/physiology, Intracellular Signaling Peptides and Proteins/metabolism, Kidney/physiology, Mechanoreceptors/physiology, Mechanotransduction, Cellular/physiology, Membrane Proteins/metabolism, Mice, Inbred C57BL, Mice, Knockout, Microscopy, Electron, Mitochondria/physiology, Mitochondrial Diseases/etiology, Mitochondrial Membranes/physiology, Podocytes/physiology, Prohibitins, Proteinuria/etiology, Repressor Proteins/deficiency, Touch/physiology",
author = "Christina Ising and Puneet Bharill and Sibylle Brinkkoetter and Sebastian Br{\"a}hler and Christina Schroeter and Sybille Koehler and Henning Hagmann and Carsten Merkwirth and Martin H{\"o}hne and M{\"u}ller, {Roman U} and Francesca Fabretti and Bernhard Schermer and Wilhelm Bloch and Dontscho Kerjaschki and Kurschat, {Christine E} and Thomas Benzing and Brinkkoetter, {Paul T}",
note = "Copyright {\textcopyright} 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.",
year = "2016",
month = may,
doi = "10.1016/j.ajpath.2015.12.018",
language = "English",
volume = "186",
pages = "1128--39",
journal = "AM J PATHOL",
issn = "0002-9440",
publisher = "Elsevier Inc.",
number = "5",

}

RIS

TY - JOUR

T1 - Prohibitin-2 Depletion Unravels Extra-Mitochondrial Functions at the Kidney Filtration Barrier

AU - Ising, Christina

AU - Bharill, Puneet

AU - Brinkkoetter, Sibylle

AU - Brähler, Sebastian

AU - Schroeter, Christina

AU - Koehler, Sybille

AU - Hagmann, Henning

AU - Merkwirth, Carsten

AU - Höhne, Martin

AU - Müller, Roman U

AU - Fabretti, Francesca

AU - Schermer, Bernhard

AU - Bloch, Wilhelm

AU - Kerjaschki, Dontscho

AU - Kurschat, Christine E

AU - Benzing, Thomas

AU - Brinkkoetter, Paul T

N1 - Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

PY - 2016/5

Y1 - 2016/5

N2 - Mitochondrial fusion is essential for maintenance of mitochondrial function and requires the prohibitin ring complex subunit prohibitin-2 (PHB2) at the mitochondrial inner membrane. Loss of the stomatin/PHB/flotillin/HflK/C (SPFH) domain containing protein PHB2 causes mitochondrial dysfunction and defective mitochondria-mediated signaling, which is implicated in a variety of human diseases, including progressive renal disease. Here, we provide evidence of additional, extra-mitochondrial functions of this membrane-anchored protein. Immunofluorescence and immunogold labeling detected PHB2 at mitochondrial membranes and at the slit diaphragm, a specialized cell junction at the filtration slit of glomerular podocytes. PHB2 coprecipitated with podocin, another SPFH domain-containing protein, essential for the assembly of the slit diaphragm protein-lipid supercomplex. Consistent with an evolutionarily conserved extra-mitochondrial function, the ortholog of PHB2 in Caenorhabditis elegans was also not restricted to mitochondria but colocalized with the mechanosensory complex that requires the podocin ortholog MEC2 for assembly. Knockdown of phb-2 partially phenocopied loss of mec-2 in touch neurons of the nematode, resulting in impaired gentle touch sensitivity. Collectively, these data indicate that, besides its established role in mitochondria, PHB2 may have an additional function in conserved protein-lipid complexes at the plasma membrane.

AB - Mitochondrial fusion is essential for maintenance of mitochondrial function and requires the prohibitin ring complex subunit prohibitin-2 (PHB2) at the mitochondrial inner membrane. Loss of the stomatin/PHB/flotillin/HflK/C (SPFH) domain containing protein PHB2 causes mitochondrial dysfunction and defective mitochondria-mediated signaling, which is implicated in a variety of human diseases, including progressive renal disease. Here, we provide evidence of additional, extra-mitochondrial functions of this membrane-anchored protein. Immunofluorescence and immunogold labeling detected PHB2 at mitochondrial membranes and at the slit diaphragm, a specialized cell junction at the filtration slit of glomerular podocytes. PHB2 coprecipitated with podocin, another SPFH domain-containing protein, essential for the assembly of the slit diaphragm protein-lipid supercomplex. Consistent with an evolutionarily conserved extra-mitochondrial function, the ortholog of PHB2 in Caenorhabditis elegans was also not restricted to mitochondria but colocalized with the mechanosensory complex that requires the podocin ortholog MEC2 for assembly. Knockdown of phb-2 partially phenocopied loss of mec-2 in touch neurons of the nematode, resulting in impaired gentle touch sensitivity. Collectively, these data indicate that, besides its established role in mitochondria, PHB2 may have an additional function in conserved protein-lipid complexes at the plasma membrane.

KW - Animals

KW - Caenorhabditis elegans Proteins

KW - Cells, Cultured

KW - HEK293 Cells

KW - Humans

KW - Intercellular Junctions/physiology

KW - Intracellular Signaling Peptides and Proteins/metabolism

KW - Kidney/physiology

KW - Mechanoreceptors/physiology

KW - Mechanotransduction, Cellular/physiology

KW - Membrane Proteins/metabolism

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Microscopy, Electron

KW - Mitochondria/physiology

KW - Mitochondrial Diseases/etiology

KW - Mitochondrial Membranes/physiology

KW - Podocytes/physiology

KW - Prohibitins

KW - Proteinuria/etiology

KW - Repressor Proteins/deficiency

KW - Touch/physiology

U2 - 10.1016/j.ajpath.2015.12.018

DO - 10.1016/j.ajpath.2015.12.018

M3 - SCORING: Journal article

C2 - 27105734

VL - 186

SP - 1128

EP - 1139

JO - AM J PATHOL

JF - AM J PATHOL

SN - 0002-9440

IS - 5

ER -