TY - JOUR
T1 - Mitochondrial control of cellular life, stress, and death
AU - Galluzzi, Lorenzo
AU - Kepp, Oliver
AU - Trojel-Hansen, Christina
AU - Kroemer, Guido
PY - 2012/10/12
Y1 - 2012/10/12
N2 - Since the discovery that mitochondrial membrane permeabilization represents a critical step in the regulation of intrinsic apoptosis, mitochondria have been viewed as pluripotent organelles, controlling cell death as well as several aspects of cell survival. Mitochondria constitute the most prominent source of ATP and are implicated in multiple anabolic and catabolic circuitries. In addition, mitochondria coordinate cell-wide stress responses, such as autophagy, and control nonapoptotic cell death routines, such as regulated necrosis. Thus, mitochondria seem to regulate a continuum of cellular functions, spanning from physiological metabolism to stress responses and death. The involvement of mitochondria in both vital and lethal processes is crucial for both embryonic and postembryonic development, as well as for the maintenance of adult tissue homeostasis. In line with this notion, primary mitochondrial defects or alterations in the signaling pathways that converge on or emanate from mitochondria underpin a large number of human diseases, including premature aging, neurodegenerative disorders, cardiovascular disorders, and cancer. Here, we provide an overview of the molecular mechanisms that enable mitochondria to sustain cell survival, coordinate stress responses, and mediate cell death, linking these pathways-whenever relevant-to cardiovascular health and disease.
AB - Since the discovery that mitochondrial membrane permeabilization represents a critical step in the regulation of intrinsic apoptosis, mitochondria have been viewed as pluripotent organelles, controlling cell death as well as several aspects of cell survival. Mitochondria constitute the most prominent source of ATP and are implicated in multiple anabolic and catabolic circuitries. In addition, mitochondria coordinate cell-wide stress responses, such as autophagy, and control nonapoptotic cell death routines, such as regulated necrosis. Thus, mitochondria seem to regulate a continuum of cellular functions, spanning from physiological metabolism to stress responses and death. The involvement of mitochondria in both vital and lethal processes is crucial for both embryonic and postembryonic development, as well as for the maintenance of adult tissue homeostasis. In line with this notion, primary mitochondrial defects or alterations in the signaling pathways that converge on or emanate from mitochondria underpin a large number of human diseases, including premature aging, neurodegenerative disorders, cardiovascular disorders, and cancer. Here, we provide an overview of the molecular mechanisms that enable mitochondria to sustain cell survival, coordinate stress responses, and mediate cell death, linking these pathways-whenever relevant-to cardiovascular health and disease.
KW - caspases
KW - cytochrome c
KW - inflammasome
KW - innate immunity
KW - reactive oxygen species
UR - http://www.scopus.com/inward/record.url?scp=84867691699&partnerID=8YFLogxK
U2 - 10.1161/CIRCRESAHA.112.268946
DO - 10.1161/CIRCRESAHA.112.268946
M3 - Review article
C2 - 23065343
AN - SCOPUS:84867691699
SN - 0009-7330
VL - 111
SP - 1198
EP - 1207
JO - Circulation Research
JF - Circulation Research
IS - 9
ER -