What is apoptosis?

From the Guidelines

Apoptosis is a highly regulated process of programmed cell death that occurs in multicellular organisms, characterized by cell shrinkage, DNA fragmentation, and the formation of apoptotic bodies, which are then engulfed by neighboring cells or immune cells without causing inflammation. This process is crucial for normal development, maintaining tissue homeostasis, and preventing diseases, as it helps shape organs during embryonic development, eliminates potentially cancerous cells, and removes cells infected by pathogens 1. The dysregulation of apoptosis can lead to various diseases, including neurodegenerative disorders, immunodeficiency, cancer, and autoimmune conditions, highlighting the importance of understanding the mechanisms underlying this process 1.

Key Characteristics of Apoptosis

• Cell shrinkage and rounding
• Chromatin condensation and nuclear fragmentation
• Formation of apoptotic bodies
• Engulfment by neighboring cells or immune cells without causing inflammation
• Regulation by complex signaling pathways involving proteins like caspases and the Bcl-2 family proteins 1

Signaling Pathways Involved in Apoptosis

• Intrinsic apoptosis: relies on mitochondrial outer membrane permeabilization (MOMP) and the activation of caspase-9 and caspase-3 1
• Extrinsic apoptosis: proceeds along with the activation of a caspase-8/caspase-3 signal transduction axis, which may also involve MOMP 1
• Regulation by Bcl-2 family proteins, including pro-apoptotic and anti-apoptotic members, and BH3-only proteins 1

Importance of Apoptosis in Disease Prevention

• Elimination of potentially cancerous cells
• Removal of cells infected by pathogens
• Maintenance of tissue homeostasis
• Prevention of autoimmune conditions and immunodeficiency 1

Consequences of Apoptosis Dysregulation

• Excessive apoptosis: contributes to neurodegenerative disorders and immunodeficiency
• Insufficient apoptosis: can lead to cancer and autoimmune conditions 1

From the Research

Definition and Importance of Apoptosis

• Apoptosis is a conserved homeostatic process critical for organ and tissue morphogenesis, development, and senescence 2.
• It is a highly regulated form of programmed cell death defined by distinct morphological and biochemical features 3.
• Apoptosis plays an important role in embryogenesis and the maintenance of cellular and tissue homeostasis in multicellular organisms 3.

Role of Apoptosis in Disease

• Apoptosis participates in the etiology of several human diseases including cancer, neurodegenerative, and autoimmune disorders 2.
• Its perturbation has been implicated in a wide range of patho-physiological stages, including autoimmune, bacterial, and viral disease, and degenerative disorders 3.
• Deregulation in apoptotic cell death machinery is a hallmark of cancer, and apoptosis alteration is responsible not only for tumor development and progression but also for tumor resistance to therapies 4.

Mechanisms of Apoptosis

• Apoptosis can be triggered by signals from within the cell, such as genotoxic stress, or by extrinsic signals, such as the binding of ligands to cell surface death receptors 4.
• The machinery responsible for killing and degradation of the cell via apoptosis is expressed constitutively and becomes activated through various stimuli 5.
• At the molecular level, apoptosis is tightly regulated and is mainly orchestrated by the activation of the aspartate-specific cysteine protease (caspase) cascade 6.

Key Regulators of Apoptosis

• Pro- and anti-apoptotic members of the Bcl-2 family regulate the mitochondrial pathway of apoptosis 6.
• Cellular stress induces pro-apoptotic Bcl-2 family members to translocate from the cytosol to the mitochondria, where they induce the release of cytochrome c 6.
• The activation of procaspase-8 and procaspase-9 are key steps in the apoptotic signaling pathways, leading to the activation of procaspase-3 and the cleavage of specific cellular substrates 6.

Apoptosis in Cancer Treatment

• Most anticancer drugs currently used in clinical oncology exploit the intact apoptotic signaling pathways to trigger cancer cell death 4.
• Defects or dysregulation of different steps of the apoptotic pathways might be an important determinant of resistance to anticancer drugs 5.
• Identification and targeting of the disabled pathway, which is most efficiently inactivated in a particular type of tumor, might be the most successful approach in the future 5.