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Sunderland Repository records the research produced by the University of Sunderland including practice-based research and theses.

Limited mitochondrial permeabilisation causes DNA-damage and genomic instability in the absence of cell death

Ichim, G, Lopez, J, Ahmed, Shafiq, Muthalagu, N, Giampazolias, E, Delgado, E, Haller, Martina, Riley, Joel S, Mason, Susan, Athineos, Dimitris, Parsons, MJ, Kooij, BVD, Bouchier-Hayes, L, Chalmers, A, Rooswinkel, R, Oberst, A, Blyth, K, Rehm, M, Murphy, D and Tait, S (2015) Limited mitochondrial permeabilisation causes DNA-damage and genomic instability in the absence of cell death. Molecular Cell, 57 (5). pp. 860-872. ISSN 1097-2765

Item Type: Article


During apoptosis, the mitochondrial outer membrane is permeabilized, leading to the release of cytochrome c that activates downstream caspases. Mitochondrial outer membrane permeabilization (MOMP) has historically been thought to occur synchronously and completely throughout a cell, leading to rapid caspase activation and apoptosis. Using a new imaging approach, we demonstrate that MOMP is not an all-or-nothing event. Rather, we find that a minority of mitochondria can undergo MOMP in a stress-regulated manner, a phenomenon we term "minority MOMP." Crucially, minority MOMP leads to limited caspase activation, which is insufficient to trigger cell death. Instead, this caspase activity leads to DNA damage that, in turn, promotes genomic instability, cellular transformation, and tumorigenesis. Our data demonstrate that, in contrast to its well-established tumor suppressor function, apoptosis also has oncogenic potential that is regulated by the extent of MOMP. These findings have important implications for oncogenesis following either physiological or therapeutic engagement of apoptosis.

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Depositing User: Paula Normington


Item ID: 6006
Identification Number:
ISSN: 1097-2765
Official URL:

Users with ORCIDS

ORCID for Shafiq Ahmed: ORCID iD

Catalogue record

Date Deposited: 12 Feb 2016 12:21
Last Modified: 04 Feb 2021 18:51


Author: Shafiq Ahmed ORCID iD
Author: G Ichim
Author: J Lopez
Author: N Muthalagu
Author: E Giampazolias
Author: E Delgado
Author: Martina Haller
Author: Joel S Riley
Author: Susan Mason
Author: Dimitris Athineos
Author: MJ Parsons
Author: BVD Kooij
Author: L Bouchier-Hayes
Author: A Chalmers
Author: R Rooswinkel
Author: A Oberst
Author: K Blyth
Author: M Rehm
Author: D Murphy
Author: S Tait

University Divisions

Faculty of Health Sciences and Wellbeing
Faculty of Health Sciences and Wellbeing > School of Pharmacy and Pharmaceutical Sciences



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