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

Citation

Hu, M and Crawford, SA and Henstridge, DC and Ng, IHW and Boey, EJH and Xu, Y and Febbraio, MA and Jans, DA and Bogoyevitch, MA, p32 protein levels are integral to mitochondrial and endoplasmic reticulum morphology, cell metabolism and survival, Biochemical Journal, 453, (3) pp. 381-391. ISSN 0264-6021 (2013) [Refereed Article]

Copyright Statement

Copyright 2013 the authors

DOI: doi:10.1042/BJ20121829

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 proteinsMfn (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.

Item Details

Item Type:Refereed Article
Keywords:endoplasmic reticulum (ER) morphology, mitochondrial metabolic activity, mitochondrial morphology, stress response, adenosine triphosphate, mitochondrial protein, mitofusin 1, mitofusin 2, p32 protein, unclassified drug, animal cell, article, human
Research Division:Biological Sciences
Research Group:Biochemistry and Cell Biology
Research Field:Cell Metabolism
Objective Division:Expanding Knowledge
Objective Group:Expanding Knowledge
Objective Field:Expanding Knowledge in the Medical and Health Sciences
UTAS Author:Henstridge, DC (Mr Darren Henstridge)
ID Code:133343
Year Published:2013
Web of Science® Times Cited:24
Deposited By:Health Sciences
Deposited On:2019-06-24
Last Modified:2019-07-31
Downloads:0

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