Opening of the MPT (mitochondrial permeability transition) pore is a critical event in mitochondrial-mediated cell death. However, with the exception of CypD (cyclophilin D), the exact molecular composition of the MPT pore remains uncertain. C1qbp (complement 1q-binding protein) has recently been hypothesized to be an essential component of the MPT pore complex. To investigate whether C1qbp indeed plays a critical role in MPT and cell death, we conducted both gain-of-function and loss-of-function experiments in MEFs (mouse embryonic fibroblasts). We first confirmed that C1qbp is a soluble protein that localizes to the mitochondrial matrix in mouse cells and tissues. Similarly, overexpression of C1qbp in MEFs using an adenovirus resulted in its exclusive localization to mitochondria. To our surprise, increased C1qbp protein levels actually suppressed H2O2-induced MPT and cell death. Antithetically, knockdown of endogenous C1qbp with siRNA (small interfering RNA) sensitized the MEFs to H2O2-induced MPT and cell death. Moreover, we found that C1qbp could directly bind to CypD. Therefore C1qbp appears to act as an endogenous inhibitor of the MPT pore, most likely through binding to CypD, and thus protects cells against oxidative stress.
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Research Article|
December 15 2010
Complement 1q-binding protein inhibits the mitochondrial permeability transition pore and protects against oxidative stress-induced death
Allison M. McGee;
Allison M. McGee
*Dalton Cardiovascular Research Center, University of Missouri-Columbia, Columbia, Missouri, 65211, U.S.A.
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Christopher P. Baines
Christopher P. Baines
1
*Dalton Cardiovascular Research Center, University of Missouri-Columbia, Columbia, Missouri, 65211, U.S.A.
†Department of Biomedical Sciences, University of Missouri-Columbia, Columbia, Missouri, 65211, U.S.A.
‡Department of Medical Pharmacology and Physiology, University of Missouri-Columbia, Columbia, Missouri, 65211, U.S.A.
1To whom correspondence should be addressed (email bainesc@missouri.edu).
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Publisher: Portland Press Ltd
Received:
September 08 2010
Revision Received:
October 12 2010
Accepted:
October 15 2010
Accepted Manuscript online:
October 15 2010
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2011 Biochemical Society
2011
Biochem J (2011) 433 (1): 119–125.
Article history
Received:
September 08 2010
Revision Received:
October 12 2010
Accepted:
October 15 2010
Accepted Manuscript online:
October 15 2010
Citation
Allison M. McGee, Christopher P. Baines; Complement 1q-binding protein inhibits the mitochondrial permeability transition pore and protects against oxidative stress-induced death. Biochem J 1 January 2011; 433 (1): 119–125. doi: https://doi.org/10.1042/BJ20101431
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