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Apoptosis of cells lacking mitochondrial DNA

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Abstract

The mitochondrial genome of animals encodes a few subcomponents of the respiratory chain complexes I, III and IV, whereas nuclear DNA encodes the overwhelming majority, both in quantitative and qualitative terms, of mitochondrial proteins. Complete depletion of mitochondrial DNA (mtDNA) can be achieved by culturing cells in the presence of inhibitors of mtDNA replication or mitochondrial protein synthesis, giving rise to mutant cells (ϱ∘ cells) which carry morphological near-to-intact mitochondria with respiratory defects. Such cells can be used to study the impact of mitochondrial respiration on apoptosis. ϱ∘ cells do not undergo cell death in response to determined stimuli, yet they conserve their potential to undergo full-blown apoptosis in many experimental systems. This indicates that mtDNA and associated functions (in particular mitochondrial respiration) are irrelevant to apoptosis execution. However, the finding that mtDNA-deficient mitochondria can undergo apoptosis does not argue against the involvement of mitochondria in the apoptotic process, since mitochondria from ϱ∘ cells conserve most of their functions including those involved in the execution of the death programme: permeability transition and release of one or several intermembrane proteins causing nuclear apoptosis.

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Authors and Affiliations

  1. Centre National de la Recherche Scientifique-UPR42O, 19 rue Guy Môquet, B.P.8, F-94801, Villejuif, France

    P. Marchetti, N. Zamzami, S. A. Susin, P. X. Petit & G. Kroemer

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  1. P. Marchetti
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  2. N. Zamzami
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  3. S. A. Susin
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  4. P. X. Petit
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  5. G. Kroemer
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Additional information

Supported by ARC, ANRS, CNRS, FRM, Fondation de France, INSERM, NATO, Ligue contre le Cancer Ministère de la Recherche et de l'Industrie (France), and Sidaction (to GK). SAS receives a fellowship from the Spanish Government (Ministerio de Ciencia y Educación).

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Marchetti, P., Zamzami, N., Susin, S.A. et al. Apoptosis of cells lacking mitochondrial DNA. Apoptosis 1, 119–125 (1996). https://doi.org/10.1007/BF01321017

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