title: Methods for the assessment of mitochondrial membrane permeabilization in apoptosis.
abstract: Mitochondrial membrane permeabilization (MMP) is considered as the "point-of-no-return" in numerous models of programmed cell death. Indeed, mitochondria determine the intrinsic pathway of apoptosis, and play a major role in the extrinsic route as well. MMP affects the inner and outer mitochondrial membranes (IM and OM, respectively) to a variable degree. OM permeabilization culminates in the release of proteins that normally are confined in the mitochondrial intermembrane space (IMS), including caspase activators (e.g. cytochrome c) and caspase-independent death effectors (e.g. apoptosis-inducing factor). Partial IM permeabilization disrupts mitochondrial ion and volume homeostasis and dissipates the mitochondrial transmembrane potential (DeltaPsi(m)). The assessment of early mitochondrial alterations allows for the identification of cells that are committed to die but have not displayed yet the apoptotic phenotype. Several techniques to measure MMP by cytofluorometry and fluorescence microscopy have been developed. Here, we summarize the currently available methods for the detection of MMP, and provide a comparative analysis of these techniques.
authors.affiliation: INSERM U848, Institut Gustave Roussy PR 1, 30 rue Camille Desmoulins, F-94805 Villejuif, France.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Galluzzi
authors.forename: Naoufal
authors.initials: N
authors.lastname: Zamzami
authors.forename: Thibault
authors.initials: T
authors.lastname: de La Motte Rouge
authors.forename: Christophe
authors.initials: C
authors.lastname: Lemaire
authors.forename: Catherine
authors.initials: C
authors.lastname: Brenner
authors.forename: Guido
authors.initials: G
authors.lastname: Kroemer
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D006801:Humans; D008564:Membrane Potentials / Q000502:physiology*; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000378:metabolism*; D000083162:Mitochondrial Permeability Transition Pore; D010539:Permeability
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore