Universität zu Köln

Ising, Christina ORCID: 0000-0002-7267-3488, Bharill, Puneet, Brinkkoetter, Sibylle, Braehler, Sebastian, Schroeter, Christina, Koehler, Sybille, Hagmann, Henning, Merkwirth, Carsten ORCID: 0000-0001-8895-3495, Hoehne, Martin, Mueller, Roman U., Fabretti, Francesca, Schermer, Bernhard ORCID: 0000-0002-5194-9000, Bloch, Wilhelm, Kerjaschki, Dontscho, Kurschat, Christine E., Benzing, Thomas and Brinkkoetter, Paul T. (2016). Prohibitin-2 Depletion Unravels Extra-Mitochondrial Functions at the Kidney Filtration Barrier. Am. J. Pathol., 186 (5). S. 1128 - 1140. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1525-2191

Full text not available from this repository.

Abstract

Mitochondrial fusion is essential for maintenance of mitochondrial function and requires the prohibitin ring complex subunit prohibitin-2 (PHB2) at the mitochondria inner membrane. Loss of the stomatin/PHB/flotitlin/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-mitochondria functions of this membrane-anchored protein. Immunofluorescence and immunogold labeling detected PHB2 at mitochondria 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-mitochondria 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Ising, Christina UNSPECIFIED orcid.org/0000-0002-7267-3488 UNSPECIFIED Bharill, Puneet UNSPECIFIED UNSPECIFIED UNSPECIFIED Brinkkoetter, Sibylle UNSPECIFIED UNSPECIFIED UNSPECIFIED Braehler, Sebastian UNSPECIFIED UNSPECIFIED UNSPECIFIED Schroeter, Christina UNSPECIFIED UNSPECIFIED UNSPECIFIED Koehler, Sybille UNSPECIFIED UNSPECIFIED UNSPECIFIED Hagmann, Henning UNSPECIFIED UNSPECIFIED UNSPECIFIED Merkwirth, Carsten UNSPECIFIED orcid.org/0000-0001-8895-3495 UNSPECIFIED Hoehne, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Mueller, Roman U. UNSPECIFIED UNSPECIFIED UNSPECIFIED Fabretti, Francesca UNSPECIFIED UNSPECIFIED UNSPECIFIED Schermer, Bernhard UNSPECIFIED orcid.org/0000-0002-5194-9000 UNSPECIFIED Bloch, Wilhelm UNSPECIFIED UNSPECIFIED UNSPECIFIED Kerjaschki, Dontscho UNSPECIFIED UNSPECIFIED UNSPECIFIED Kurschat, Christine E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Benzing, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Brinkkoetter, Paul T. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-277484
DOI:	10.1016/j.ajpath.2015.12.018
Journal or Publication Title:	Am. J. Pathol.
Volume:	186
Number:	5
Page Range:	S. 1128 - 1140
Date:	2016
Publisher:	ELSEVIER SCIENCE INC
Place of Publication:	NEW YORK
ISSN:	1525-2191
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language TOUCH RECEPTOR NEURONS; CAENORHABDITIS-ELEGANS; C-ELEGANS; CRISTAE MORPHOGENESIS; CELL-PROLIFERATION; NEPHROTIC SYNDROME; SLIT DIAPHRAGM; PODOCYTES; APOPTOSIS; PODOCIN Multiple languages Pathology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/27748