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Mitochondrial outer membrane permeabilization: a focus on the role of mitochondrial membrane structural organization

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Abstract

Apoptosis is important in regulating cell death turnover and is mediated by the intrinsic and death receptor-based extrinsic pathways which converge at the mitochondrial outer membrane (MOM) leading to mitochondrial outer membrane permeabilization (MOMP). MOMP results in the release of apoptotic proteins that further activate the downstream pathway of apoptosis. Thus, tight regulation of MOMP is crucial in controlling apoptosis, and a lack of control may lead to tissue and organ malformation and the development of cancers. Despite a growing number of studies focusing on the structure and activity of the proteins involved in mediating MOMP, such as the Bcl-2 family proteins, the mechanism of MOMP is not well understood. In particular, the crucial role of the various structural properties and changes in lipid components of the MOM in mediating the recruitment and activation of different Bcl-2 proteins remains poorly understood. Furthermore, the factors that control the changes in mitochondrial membrane integrity from the initiation to the final disruption of MOM have yet to be clearly defined. In this review, we provide an overview of studies that focus on the mitochondrial membrane with a biophysical analysis of the interactions of the Bcl-2 proteins with the mitochondrial membrane.

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Acknowledgements

The financial support of the National Health & Medical Research Council (#1084648) is gratefully acknowledged.

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Author notes

  1. Siti Haji Suhaili and Hamed Karimian contributed equally to this work

Authors and Affiliations

  1. Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Wellington Rd, Clayton, VIC, 3800, Australia

    Siti Haji Suhaili, Hamed Karimian, Matthew Stellato, Tzong-Hsien Lee & Marie-Isabel Aguilar

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  1. Siti Haji Suhaili
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Correspondence to Marie-Isabel Aguilar.

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Siti Haji Suhaili declares that she has no conflicts of interest. Hamed Karimian declares that he has no conflicts of interest. Matthew Stellato declares that he has no conflicts of interest. Tzong-Hsien Lee declares that he has no conflicts of interest. Marie-Isabel Aguilar declares that she has no conflicts of interest.

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This article does not contain any studies with human participants or animals performed by any of the authors.

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This article is part of a Special Issue on ‘IUPAB Edinburgh Congress’ edited by Damien Hall.

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Suhaili, S.H., Karimian, H., Stellato, M. et al. Mitochondrial outer membrane permeabilization: a focus on the role of mitochondrial membrane structural organization. Biophys Rev 9, 443–457 (2017). https://doi.org/10.1007/s12551-017-0308-0

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