Autophagy, Apoptosis, Mitoptosis and Necrosis: Interdependence Between Those Pathways and Effects on Cancer
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REVIEW
Autophagy, Apoptosis, Mitoptosis and Necrosis: Interdependence Between Those Pathways and Effects on Cancer Wiem Chaabane • Sırma D. User • Mohamed El-Gazzah • Roman Jaksik Elaheh Sajjadi • Joanna Rzeszowska-Wolny • Marek J. Łos
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Received: 22 May 2012 / Accepted: 6 September 2012 / Published online: 11 December 2012 Ó L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland 2012
Abstract Cell death is a fundamental ingredient of life. Thus, not surprisingly more than one form of cell death exists. Several excellent reviews on various forms of cell death have already been published but manuscripts describing interconnection and interdependence between such processes are uncommon. Here, what follows is a brief introduction on all three classical forms of cell death, followed by a more detailed insight into the role of p53, the master regulator of apoptosis, and other forms of cell death. While discussing p53 and also the role of caspases in cell death forms, we offer insight into the interplay between autophagy and apoptosis, or necrosis, where autophagy may initially serve pro-survival functions. The review moves
W. Chaabane S. D. User M. J. Łos (&) Division of Cell Biology, Department Clinical and Experimental Medicine (IKE), and Integrative Regenerative Medicine Center (IGEN), Linko¨ping University, Cell Biology Building, Level 10, 581 85 Linko¨ping, Sweden e-mail: [email protected]; [email protected] W. Chaabane M. El-Gazzah Department of Biology, Faculty of Sciences, Tunis University, Tunis, Tunisia S. D. User Faculty Art and Science, Middle East Technical University, Ankara, Turkey R. Jaksik J. Rzeszowska-Wolny Biosystems Group, Institute of Automatic Control, Silesian University of Technology, Gliwice, Poland E. Sajjadi Rehabilitation School, Tehran University of Medical Sciences, Tehran, Iran M. J. Łos BioApplications Enterprises, Winnipeg, MB, Canada
further to present some details about less researched forms of programmed cell death, namely necroptosis, necrosis and mitoptosis. These ‘‘mixed’’ forms of cell death allow us to highlight the interconnected nature of cell death forms, particularly apoptosis and necrosis. The interdependence between apoptosis, autophagy and necrosis, and their significance for cancer development and treatment are also analyzed in further parts of the review. In the concluding parts, the afore-mentioned issues will be put in perspective for the development of novel anti-cancer therapies. Keywords AMPK Hsp-70 Mdm2 Mitochondria mTOR RIPK PARP-1 PKC-delta TNF VHL Abbreviations AML Acute myeloid leukemia AMPK 5-Prime-AMP-activated protein kinase Apaf1 Apoptotic protease activating factor-1 ATG Autophagy related gene BH Bcl2-homology DIABLO Direct IAP-bind protein with low pI DISC Death-inducing signaling complex DRAM Damage-regulated autophagy modulator eEF2-kinase Elongation factor kinase-2 Hsp-70 Heat shock protein 70 Mcl-1 Myeloid cell leukemia-1 Mdm2 Murine double minute 2 mTOR Mammalian target of rapamycin Nec-1 Necrostat
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