p32 protein levels are integral to mitochondrial and endoplasmic reticulum morphology, cell metabolism and survival

Mengjie Hu, Simon A Crawford, Darren Colin Henstridge, Ivan Hong Wee Ng, Esther JH Boey, Yuekang Xu, Mark Anthony Febbraio, David Andrew Jans, Marie Ann Bogoyevitch

Research output: Contribution to journalArticleResearchpeer-review

24 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)381-391
Number of pages11
JournalBiochemical Journal
Volume453
Issue number3
DOIs
Publication statusPublished - 2013

Cite this

@article{b59603fd1c70449b91426cbab59f3270,
title = "p32 protein levels are integral to mitochondrial and endoplasmic reticulum morphology, cell metabolism and survival",
abstract = "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.",
author = "Mengjie Hu and Crawford, {Simon A} and Henstridge, {Darren Colin} and Ng, {Ivan Hong Wee} and Boey, {Esther JH} and Yuekang Xu and Febbraio, {Mark Anthony} and Jans, {David Andrew} and Bogoyevitch, {Marie Ann}",
year = "2013",
doi = "10.1042/BJ20121829",
language = "English",
volume = "453",
pages = "381--391",
journal = "Biochemical Journal",
issn = "0264-6021",
publisher = "Portland Press",
number = "3",

}

p32 protein levels are integral to mitochondrial and endoplasmic reticulum morphology, cell metabolism and survival. / Hu, Mengjie; Crawford, Simon A; Henstridge, Darren Colin; Ng, Ivan Hong Wee; Boey, Esther JH; Xu, Yuekang; Febbraio, Mark Anthony; Jans, David Andrew; Bogoyevitch, Marie Ann.

In: Biochemical Journal, Vol. 453, No. 3, 2013, p. 381-391.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - p32 protein levels are integral to mitochondrial and endoplasmic reticulum morphology, cell metabolism and survival

AU - Hu, Mengjie

AU - Crawford, Simon A

AU - Henstridge, Darren Colin

AU - Ng, Ivan Hong Wee

AU - Boey, Esther JH

AU - Xu, Yuekang

AU - Febbraio, Mark Anthony

AU - Jans, David Andrew

AU - Bogoyevitch, Marie Ann

PY - 2013

Y1 - 2013

N2 - 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.

AB - 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.

UR - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3727215/pdf/bj4530381.pdf

U2 - 10.1042/BJ20121829

DO - 10.1042/BJ20121829

M3 - Article

VL - 453

SP - 381

EP - 391

JO - Biochemical Journal

JF - Biochemical Journal

SN - 0264-6021

IS - 3

ER -