, Volume 12, Issue 5, pp 803–813 | Cite as

Methods for the assessment of mitochondrial membrane permeabilization in apoptosis

  • Lorenzo Galluzzi
  • Naoufal Zamzami
  • Thibault de La Motte Rouge
  • Christophe Lemaire
  • Catherine Brenner
  • Guido KroemerEmail author


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 (ΔΨm). 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.


Apoptosis FACS Fluorescence microscopy Fluorochromes Mitochondrial membrane permeabilization Mitochondrial transmembrane potential 



proton nuclear magnetic resonance


mitochondrial transmembrane potential


apoptosis-inducing factor


adenine nucleotide translocase


apoptosis protease activating factor 1


Bcl-2 homology domain 3




cyclophilin D

Cyt c

cytochrome c


3,3′dihexiloxalocarbocyanine iodide


enzyme-linked immunosorbent assay


fluorescence-activated cell sorter


forward scatter


green fluorescent protein


human immunodeficiency virus type 1


high-pressure liquid chromatography


heat shock protein of 60 kDa


5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolcarbocyanine iodide


Omi stress-regulated endoprotease/High temperature requirement protein A 2


permeability transition


permeability transition pore complex

Rh 123

rhodamine 123


second mitochondria-derived activator of caspase/direct IAP binding protein with a low pI


side scatter


truncated Bid


tetramethylrhodamine ethyl ester


tetramethylrhodamine methyl ester


voltage-dependent anion channel


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Copyright information

© Springer Science + Business Media, LLC 2007

Authors and Affiliations

  • Lorenzo Galluzzi
    • 1
    • 2
    • 3
  • Naoufal Zamzami
    • 1
    • 2
    • 3
  • Thibault de La Motte Rouge
    • 1
    • 2
    • 3
  • Christophe Lemaire
    • 4
  • Catherine Brenner
    • 4
  • Guido Kroemer
    • 1
    • 2
    • 3
    • 5
    Email author
  1. 1.INSERM, U848VillejuifFrance
  2. 2.Institut Gustave RoussyVillejuifFrance
  3. 3.Faculté de Médecine-Université Paris-Sud XIVillejuifFrance
  4. 4.Université de Versailles/SQY-CNRS UMR 8159VersaillesFrance
  5. 5.INSERM, U848, Institut Gustave Roussy, PR138 rue Camille DesmoulinsVillejuifFrance

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