Role of mitochondria as the gardens of cell death |
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Authors: | Ryungsa Kim Manabu Emi Kazuaki Tanabe |
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Institution: | (1) International Radiation Information Center, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi Minami-ku, Hiroshima 734-8553, Japan;(2) Depertment of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan |
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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. |
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Keywords: | Mitochondria Apoptosis Autophagy Endoplasmic reticulum Lysosome |
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