, Volume 62, Issue 3, pp 175–188 | Cite as

Cell death in mammalian cell culture: molecular mechanisms and cell line engineering strategies

  • Britta Krampe
  • Mohamed Al-RubeaiEmail author


Cell death is a fundamentally important problem in cell lines used by the biopharmaceutical industry. Environmental stress, which can result from nutrient depletion, by-product accumulation and chemical agents, activates through signalling cascades regulators that promote death. The best known key regulators of death process are the Bcl-2 family proteins which constitute a critical intracellular checkpoint of apoptosis cell death within a common death pathway. Engineering of several members of the anti-apoptosis Bcl-2 family genes in several cell types has extended the knowledge of their molecular function and interaction with other proteins, and their regulation of cell death. In this review, we describe the various modes of cell death and their death pathways at molecular and organelle level and discuss the relevance of the growing knowledge of anti-apoptotic engineering strategies to inhibit cell death and increase productivity in mammalian cell culture.


Bcl-2 Apoptosis Autophagy Cell engineering Signalling pathways Cell death 





Apoptosis-inducing factors


Adenine nucleotide translocator


Protein kinase B


Autophagy-related proteins


Apoptosis, caspase activation inhibitor


Apoptotic protease activation factor 1


Jun oncogene


Bcl-2-associated agonist of cell death


Bcl-2-antagonist/killer 1


Bcl-2-associated X protein


B-cell lymphoma


Bcl-2 related gene, long isoform


BH3 interacting domain death agonist


Bcl-2-like 11


Bcl-2-related ovarian killer


v-myc myelocytomatosis viral oncogene homolog


AMP responsive element binding protein 1


Endoplasmic reticulum


Eukaryotic transcription factor 4


Eukaryotic transcription factor 1


Fas-associated death domain


Fas ligand


Myeloid cell leukemia sequence 1 (Bcl2-related)


Target of rapamycin


Mitochondrial outer membrane permeabilization


PMA-induced protein


Nuclear receptor subfamily 4


Phosphoinositide 3-kinase


Protein kinase B


Permeability transition pores


p53-upregulated modulator of apoptosis


Cyclin dependent kinase inhibitor protein 1B


Second mitochondria-derived activator of caspases/direct IAP-bind protein with low pI


Tumour necrosis factor


TNF-related apoptosis-inducing ligand


Voltage dependent anion channel


Unfolded protein response


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© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  1. 1.School of Chemical and Bioprocess Engineering, and Conway Institute of Biomolecular & Biomedical ResearchUniversity College DublinBelfield, Dublin 4Republic of Ireland

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