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p32 protein levels are integral to mitochondrial and endoplasmic reticulum morphology, cell metabolism and survival
p32 [also known as HABP1 (hyaluronan-binding protein 1), gC1qR (receptor for globular head domains complement 1q) or C1qbp (complement 1q-binding protein)] has been shown previously to have both mitochondrial and non-mitochondrial localization and functions. In the present study, we show for the fir...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Portland Press Ltd.
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3727215/ https://www.ncbi.nlm.nih.gov/pubmed/23692256 http://dx.doi.org/10.1042/BJ20121829 |
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author | Hu, MengJie Crawford, Simon A. Henstridge, Darren C. Ng, Ivan H. W. Boey, Esther J. H. Xu, Yuekang Febbraio, Mark A. Jans, David A. Bogoyevitch, Marie A. |
author_facet | Hu, MengJie Crawford, Simon A. Henstridge, Darren C. Ng, Ivan H. W. Boey, Esther J. H. Xu, Yuekang Febbraio, Mark A. Jans, David A. Bogoyevitch, Marie A. |
author_sort | Hu, MengJie |
collection | PubMed |
description | p32 [also known as HABP1 (hyaluronan-binding protein 1), gC1qR (receptor for globular head domains complement 1q) or C1qbp (complement 1q-binding protein)] has been shown previously to have both mitochondrial and non-mitochondrial localization and functions. In the present study, we show for the first time that endogenous p32 protein is a mitochondrial protein in HeLa cells under control and stress conditions. In defining the impact of altering p32 levels in these cells, we demonstrate that the overexpression of p32 increased mitochondrial fibrils. Conversely, siRNA-mediated p32 knockdown enhanced mitochondrial fragmentation accompanied by a loss of detectable levels of the mitochondrial fusion mediator proteins Mfn (mitofusin) 1 and Mfn2. More detailed ultrastructure analysis by transmission electron microscopy revealed aberrant mitochondrial structures with less and/or fragmented cristae and reduced mitochondrial matrix density as well as more punctate ER (endoplasmic reticulum) with noticeable dissociation of their ribosomes. The analysis of mitochondrial bioenergetics showed significantly reduced capacities in basal respiration and oxidative ATP turnover following p32 depletion. Furthermore, siRNA-mediated p32 knockdown resulted in differential stress-dependent effects on cell death, with enhanced cell death observed in the presence of hyperosmotic stress or cisplatin treatment, but decreased cell death in the presence of arsenite. Taken together, our studies highlight the critical contributions of the p32 protein to the morphology of mitochondria and ER under normal cellular conditions, as well as important roles of the p32 protein in cellular metabolism and various stress responses. |
format | Online Article Text |
id | pubmed-3727215 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Portland Press Ltd. |
record_format | MEDLINE/PubMed |
spelling | pubmed-37272152013-08-06 p32 protein levels are integral to mitochondrial and endoplasmic reticulum morphology, cell metabolism and survival Hu, MengJie Crawford, Simon A. Henstridge, Darren C. Ng, Ivan H. W. Boey, Esther J. H. Xu, Yuekang Febbraio, Mark A. Jans, David A. Bogoyevitch, Marie A. Biochem J Research Article p32 [also known as HABP1 (hyaluronan-binding protein 1), gC1qR (receptor for globular head domains complement 1q) or C1qbp (complement 1q-binding protein)] has been shown previously to have both mitochondrial and non-mitochondrial localization and functions. In the present study, we show for the first time that endogenous p32 protein is a mitochondrial protein in HeLa cells under control and stress conditions. In defining the impact of altering p32 levels in these cells, we demonstrate that the overexpression of p32 increased mitochondrial fibrils. Conversely, siRNA-mediated p32 knockdown enhanced mitochondrial fragmentation accompanied by a loss of detectable levels of the mitochondrial fusion mediator proteins Mfn (mitofusin) 1 and Mfn2. More detailed ultrastructure analysis by transmission electron microscopy revealed aberrant mitochondrial structures with less and/or fragmented cristae and reduced mitochondrial matrix density as well as more punctate ER (endoplasmic reticulum) with noticeable dissociation of their ribosomes. The analysis of mitochondrial bioenergetics showed significantly reduced capacities in basal respiration and oxidative ATP turnover following p32 depletion. Furthermore, siRNA-mediated p32 knockdown resulted in differential stress-dependent effects on cell death, with enhanced cell death observed in the presence of hyperosmotic stress or cisplatin treatment, but decreased cell death in the presence of arsenite. Taken together, our studies highlight the critical contributions of the p32 protein to the morphology of mitochondria and ER under normal cellular conditions, as well as important roles of the p32 protein in cellular metabolism and various stress responses. Portland Press Ltd. 2013-07-12 2013-08-01 /pmc/articles/PMC3727215/ /pubmed/23692256 http://dx.doi.org/10.1042/BJ20121829 Text en © 2013 The author(s) has paid for this article to be freely available under the terms of the Creative Commons Attribution Licence (CC-BY)(http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Hu, MengJie Crawford, Simon A. Henstridge, Darren C. Ng, Ivan H. W. Boey, Esther J. H. Xu, Yuekang Febbraio, Mark A. Jans, David A. Bogoyevitch, Marie A. p32 protein levels are integral to mitochondrial and endoplasmic reticulum morphology, cell metabolism and survival |
title | p32 protein levels are integral to mitochondrial and endoplasmic reticulum morphology, cell metabolism and survival |
title_full | p32 protein levels are integral to mitochondrial and endoplasmic reticulum morphology, cell metabolism and survival |
title_fullStr | p32 protein levels are integral to mitochondrial and endoplasmic reticulum morphology, cell metabolism and survival |
title_full_unstemmed | p32 protein levels are integral to mitochondrial and endoplasmic reticulum morphology, cell metabolism and survival |
title_short | p32 protein levels are integral to mitochondrial and endoplasmic reticulum morphology, cell metabolism and survival |
title_sort | p32 protein levels are integral to mitochondrial and endoplasmic reticulum morphology, cell metabolism and survival |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3727215/ https://www.ncbi.nlm.nih.gov/pubmed/23692256 http://dx.doi.org/10.1042/BJ20121829 |
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