The pathophysiology of mitochondrial cell death

Douglas R. Green, Guido Kroemer

    Research output: Contribution to journalReview articlepeer-review

    2959 Citations (Scopus)

    Abstract

    In the mitochondrial pathway of apoptosis, caspase activation is closely linked to mitochondrial outer membrane permeabilization (MOMP). Numerous pro-apoptotic signal-transducing molecules and pathological stimuli converge on mitochondria to induce MOMP. The local regulation and execution of MOMP involve proteins from the Bcl-2 family, mitochondrial lipids, proteins that regulate bioenergetic metabolite flux, and putative components of the permeability transition pore. MOMP is lethal because it results in the release of caspase-activating molecules and caspase-independent death effectors, metabolic failure in the mitochondria, or both. Drugs designed to suppress excessive MOMP may avoid pathological cell death, and the therapeutic induction of MOMP may restore apoptosis in cancer cells in which it is disabled. The general rules governing the pathophysiology of MOMP and controversial issues regarding its regulation are discussed.

    Original languageEnglish
    Pages (from-to)626-629
    Number of pages4
    JournalScience
    Volume305
    Issue number5684
    DOIs
    Publication statusPublished - 30 Jul 2004

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