The mitochondrial membrane potential (deltapsi(m)) in apoptosis; an update.
Mitochondrial dysfunction has been shown to participate in the induction of apoptosis and has even been suggested to be central to the apoptotic pathway. Indeed, opening of the mitochondrial permeability transition pore has been demonstrated to induce depolarization of the transmembrane potential (deltapsi(m)), release of apoptogenic factors and loss of oxidative phosphorylation. In some apoptotic systems, loss of deltapsi(m) may be an early event in the apoptotic process. However, there are emerging data suggesting that, depending on the model of apoptosis, the loss of deltapsi(m) may not be an early requirement for apoptosis, but on the contrary may be a consequence of the apoptotic-signaling pathway. Furthermore, to add to these conflicting data, loss of deltapsi(m) has been demonstrated to not be required for cytochrome c release, whereas release of apoptosis inducing factor AIF is dependent upon disruption of deltapsi(m) early in the apoptotic pathway. Together, the existing literature suggests that depending on the cell system under investigation and the apoptotic stimuli used, dissipation of deltapsi(m) may or may not be an early event in the apoptotic pathway. Discrepancies in this area of apoptosis research may be attributed to the fluorochromes used to detect deltapsi(m). Differential degrees of sensitivity of these fluorochromes exist, and there are also important factors that contribute to their ability to accurately discriminate changes in deltapsi(m).
Ly
J D
JD
Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Building 13D, Melbourne 3800, Australia.
Grubb
D R
DR
Lawen
A
A
D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D004396:Coloring Agents / Q000494:pharmacology; D045304:Cytochromes c / Q000378:metabolism; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D007473:Ion Channels / Q000502:physiology*; D008564:Membrane Potentials; D008928:Mitochondria / Q000502:physiology*; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D008954:Models, Biological; D010539:Permeability; D011487:Protein Conformation; D015398:Signal Transduction
D004396:Coloring Agents; D007473:Ion Channels; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D045304:Cytochromes c