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Mitochondrial Regulation of Apoptosis

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Mitochondrial DNA Mutations in Aging, Disease and Cancer

Abstract

Physiological cell death (PCD) constitutes a strictly regulated process which is responsible for the removal of superfluous, aged, or damaged cells. An abnormal resistance to PCD entails malformations, autoimmune disease, or cancer due to the persistence of superfluous, self-specific, or mutated cells, respectively. In contrast, enhanced removal of cells by PCD participates in acute diseases (intoxications, septic shock, anoxia), as well as in chronic pathologies (neurodegenerative and neuromuscular diseases, AIDS). PCD, whose morphological and biochemical phenotype is referred to as “apoptosis”, is characterized by the action of catabolic enzymes, mostly proteases and nucleases, within the limits of a near-to-intact plasma membrane. Thus, the cell actively contributes to its removal and undergoes a series of stereotyped biochemical and ultrastructural alterations (Table 8.1). Apoptosis is the final outcome of multiple different death-inducing pathways. In mammalian cells, such apoptosis-triggering stimuli include interventions on second messenger systems, ligation of certain receptors (Fas/APO-1/CD95, TGF-R, TNF-R, etc.) or, in the case of obligate growth factor receptors, the absence of receptor occupancy. In addition, suboptimal culture conditions (lack of essential compounds, shortage of nutrients, deficiency of oxygen), mild physical damage (radiotherapy), and numerous toxins (chemotherapy and toxins stricto sensu) can provoke apoptosis.1–5 Thus, apoptosis can result both from physiological and from pathological triggers. In vivo, cells undergoing apoptosis are recognized and removed by phagocytes before they undergo lysis. Phagocytic recognition of apoptotic cells is facilitated by characteristic changes in plasma membrane structure, namely the loss of plasma membrane asymmetry with a consequent aberrant exposure of phosphatidylserine (PS) residues (normally only located in the inner membrane leaflet) on the cell surface.

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  1. Patrice X. Petit
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  2. Guido Kroemer
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  1. The Division of Experimental Therapeutics and Radiation Oncology, Johns Hopkins Oncology Center and Department of Environmental Health, Johns Hopkins School of Public Health, 600 N. Wolfe Street, Room 2-121, 21287, Baltimore, Maryland, USA

    Keshav K. Singh Ph.D.

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Petit, P.X., Kroemer, G. (1998). Mitochondrial Regulation of Apoptosis. In: Singh, K.K. (eds) Mitochondrial DNA Mutations in Aging, Disease and Cancer. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-12509-0_8

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