Cancer Chemotherapy and Pharmacology

, Volume 57, Issue 5, pp 545–553 | Cite as

Role of mitochondria as the gardens of cell death

  • Ryungsa KimEmail author
  • Manabu Emi
  • Kazuaki Tanabe


Mitochondria play a crucial role in regulating cell death, which is mediated by outer membrane permeabilization in response to death triggers such as DNA damage and growth factor deprivation. Mitochondrial membrane permeabilization induces the release of cytochrome c, Smac/DIABLO, and AIF, which are regulated by proapoptotic and antiapoptotic proteins such as Bax/Bak and Bcl-2/xL in caspase-dependent and caspase-independent apoptosis pathways. Mitochondrial dysfunction is mediated in two ways. The first is by increased calcium in mitochondria derived from endoplasmic reticulum (ER); this calcium increase is regulated by Bcl-2 and Bax through the ER-mitochondria connection and the unfolded protein response in the ER. The second is by the lysosomal enzyme cathepsin, which activates Bid through lysosome–mitochondria cross-signaling. The genomic responses in intracellular organelles after DNA damage are controlled and amplified in the cross-signaling via mitochondria; such signals induce apoptosis, autophagy, and other cell death pathways. This review discusses the recent advancements in understanding the molecular mechanism of mitochondria-mediated cell death.


Mitochondria Apoptosis Autophagy Endoplasmic reticulum Lysosome 



Second mitochondria-derived activator of caspase


Direct inhibitor of apoptosis-binding protein with low pI


Apoptosis-inducing factor


Mitochondrial membrane permeabilization


Voltage-dependent anion channel


Adenine nucleotide translocator


Reactive oxygen species


Endoplasmic reticulum


Programmed cell death


Sarcoplasmic/ER Ca2+ ATPase


Unfolded protein response


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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  1. 1.International Radiation Information Center, Research Institute for Radiation Biology and MedicineHiroshima UniversityHiroshimaJapan
  2. 2.Depertment of Surgical Oncology, Research Institute for Radiation Biology and MedicineHiroshima UniversityHiroshimaJapan

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