Cancer Chemotherapy and Pharmacology

, Volume 57, Issue 5, pp 545–553

Role of mitochondria as the gardens of cell death

Review

DOI: 10.1007/s00280-005-0111-7

Cite this article as:
Kim, R., Emi, M. & Tanabe, K. Cancer Chemother Pharmacol (2006) 57: 545. doi:10.1007/s00280-005-0111-7

Abstract

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.

Keywords

MitochondriaApoptosisAutophagyEndoplasmic reticulumLysosome

Abbreviations

Smac

Second mitochondria-derived activator of caspase

DIABLO

Direct inhibitor of apoptosis-binding protein with low pI

AIF

Apoptosis-inducing factor

MMP

Mitochondrial membrane permeabilization

VDAC

Voltage-dependent anion channel

ANT

Adenine nucleotide translocator

ROS

Reactive oxygen species

ER

Endoplasmic reticulum

PCD

Programmed cell death

SERCA

Sarcoplasmic/ER Ca2+ ATPase

UPR

Unfolded protein response

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