Role of mitochondrial ion channels in cell death.
Ion channels located in the outer and inner mitochondrial membranes are key regulators of cellular signaling for life and death. Permeabilization of mitochondrial membranes is one of the most critical steps in the progression of several cell death pathways. The mitochondrial apoptosis-induced channel (MAC) and the mitochondrial permeability transition pore (mPTP) play major roles in these processes. Here, the most recent progress and current perspectives about the roles of MAC and mPTP in mitochondrial membrane permeabilization during cell death are presented. The crosstalk signaling of MAC and mPTP formation/activation mediated by cytosolic Ca(2+) signaling, Bcl-2 family proteins, and other mitochondrial ion channels is also discussed. Understanding the mechanisms that regulate opening and closing of MAC and mPTP has revealed new therapeutic targets that potentially could control cell death in pathologies such as cancer, ischemia/reperfusion injuries, and neurodegenerative diseases.
Ryu
Shin-Young
SY
Department of Basic Sciences, New York University College of Dentistry, New York, USA.
Peixoto
Pablo M
PM
Teijido
Oscar
O
Dejean
Laurent M
LM
Kinnally
Kathleen W
KW
D000818:Animals; D017209:Apoptosis; D027682:Cation Transport Proteins / Q000378:metabolism; D016923:Cell Death; D006801:Humans; D007473:Ion Channels / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D015427:Reperfusion Injury / Q000378:metabolism
D027682:Cation Transport Proteins; D007473:Ion Channels; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore