2.3 Cell Death: Apoptosis and Necrosis
2 min read•july 24, 2024
Cell death mechanisms are crucial for understanding how our bodies maintain balance and respond to injury. , a controlled process, helps shape organs and regulate the immune system. , an uncontrolled death, occurs from severe damage like burns or toxins.
These processes play vital roles in health and disease. Dysregulated cell death contributes to , neurodegenerative diseases, and autoimmune disorders. Understanding these mechanisms is key for developing treatments targeting apoptotic pathways or preventing excessive necrosis in various conditions.
Cell Death Mechanisms
Apoptosis vs necrosis
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- Apoptosis involves maintaining tissue homeostasis through controlled energy-dependent process characterized by cell shrinkage and fragmentation (embryonic development)
- Necrosis occurs as accidental or uncontrolled cell death resulting from external factors often caused by severe cellular injury characterized by cell swelling and rupture (severe burns)
Molecular mechanisms of apoptosis
- Extrinsic pathway activated by external death ligands involving death receptors (Fas, TNF receptor) leads to activation of initiator (caspase-8 or -10)
- Intrinsic pathway triggered by internal cellular stress involves mitochondrial outer membrane permeabilization releasing cytochrome c into cytosol forming apoptosome activating initiator caspase-9
- Execution phase activates effector caspases (caspase-3, -6, and -7) cleaving cellular proteins fragmenting DNA forming apoptotic bodies
Physiological roles of apoptosis
- Embryonic development removes unnecessary cells during organ formation shaping limbs and digits forming neural tube (webbed fingers)
- Immune system regulation eliminates self-reactive lymphocytes terminates immune responses maintains peripheral tolerance (autoimmune prevention)
- Tissue homeostasis balances cell proliferation and death removing damaged or potentially harmful cells (skin cell turnover)
Characteristics and causes of necrosis
- Morphological characteristics include cell swelling plasma membrane rupture release of cellular contents in surrounding tissue (tissue edema)
- Biochemical characteristics involve ATP depletion loss of ion homeostasis activation of degradative enzymes oxidative stress (cellular energy crisis)
- Potential causes encompass or hypoxia toxins or poisons extreme temperature changes mechanical trauma infections (frostbite)
Dysregulated cell death in disease
- Cancer exhibits reduced apoptosis leading to uncontrolled cell growth mutations in pro-apoptotic genes (p53) overexpression of anti-apoptotic proteins ()
- Neurodegenerative diseases show excessive apoptosis in Alzheimer's and Parkinson's diseases accumulation of misfolded proteins triggering cell death leading to neuronal loss
- Autoimmune disorders fail to eliminate self-reactive lymphocytes increase resistance to apoptosis in autoreactive cells (lupus)
- Ischemic injuries cause necrosis in heart attacks and strokes secondary damage due to inflammation (myocardial infarction)
- Therapeutic implications include targeting apoptotic pathways in cancer treatment developing neuroprotective strategies for neurodegenerative diseases (chemotherapy)
Key Terms to Review (17)
Apoptosis: Apoptosis is a programmed cell death process that occurs in multicellular organisms, allowing cells to self-destruct when they are damaged, diseased, or no longer needed. This controlled mechanism is crucial for maintaining homeostasis, development, and the elimination of potentially harmful cells, such as those that could become cancerous. By understanding apoptosis, one can appreciate its role in cellular injury, adaptations to stress, and the intricate balance between life and death at the cellular level.
Bcl-2: Bcl-2 is a crucial protein that plays a significant role in regulating apoptosis, the process of programmed cell death. By inhibiting apoptosis, Bcl-2 helps cells survive longer than they normally would, making it essential for cell life regulation. This protein is particularly relevant in the context of cancer, where its overexpression can lead to tumorigenesis by allowing malignant cells to evade the normal death signals that would typically trigger their demise.
Cancer: Cancer is a group of diseases characterized by uncontrolled cell growth and division, leading to the formation of tumors that can invade surrounding tissues and spread to other parts of the body. This process disrupts normal cellular function and can result in significant physiological changes and complications, often linked to various forms of cell death such as apoptosis and necrosis.
Caspases: Caspases are a family of cysteine proteases that play essential roles in the process of programmed cell death, also known as apoptosis. They act as key mediators that execute the death program by cleaving specific substrates, leading to cellular dismantling and ultimately cell death. Their activity is crucial not just in apoptosis but also in inflammation and cell differentiation, highlighting their importance in maintaining cellular homeostasis.
Coagulative necrosis: Coagulative necrosis is a type of tissue death characterized by the preservation of the basic tissue architecture, despite cell injury. This form of necrosis is typically seen following ischemic events or infarction, where blood supply is severely reduced or cut off, leading to the denaturation of proteins and cellular components. It commonly occurs in solid organs like the heart, kidneys, and spleen, and is marked by firm, pale tissue that retains its structure while losing cellular integrity.
Death Receptor Pathways: Death receptor pathways are specific signaling mechanisms that lead to programmed cell death, or apoptosis, through the activation of cell surface receptors known as death receptors. These receptors, such as Fas and tumor necrosis factor (TNF) receptors, initiate a cascade of intracellular events that ultimately result in the orderly elimination of damaged or unwanted cells. This process is crucial for maintaining tissue homeostasis and regulating immune responses.
Immune Response: The immune response is the body's complex defense mechanism against foreign invaders, such as pathogens, and involves the recognition and elimination of these harmful agents. This process includes both innate and adaptive immunity, with acute and chronic inflammation playing crucial roles in the immediate and long-term response to infection. The immune response also involves various white blood cells and lymphoid tissues that work together to provide protection and maintain health.
Inflammation: Inflammation is a complex biological response of the body's immune system to harmful stimuli, such as pathogens, damaged cells, or irritants. It serves as a protective mechanism to eliminate the initial cause of cell injury, clear out dead cells, and initiate tissue repair. Understanding inflammation is crucial because it underlies many pathological processes in various conditions, including hypersensitivity reactions, autoimmune disorders, and tissue repair mechanisms.
Ischemia: Ischemia refers to the inadequate blood supply to a tissue, resulting in a deficiency of oxygen and nutrients necessary for cellular metabolism. This condition can lead to cellular injury and can have widespread implications for organ function and overall health.
Lactate dehydrogenase: Lactate dehydrogenase (LDH) is an enzyme that plays a crucial role in the conversion of lactate to pyruvate and vice versa, facilitating anaerobic metabolism. This enzyme is present in many tissues throughout the body and is important for energy production, especially during conditions of low oxygen. LDH levels can serve as significant biomarkers in various clinical settings, indicating tissue damage or hypoxia.
Liquefactive necrosis: Liquefactive necrosis is a type of tissue death where the affected area becomes transformed into a liquid viscous mass. This process typically occurs in response to bacterial infections or brain ischemia, resulting in the release of enzymes that liquefy the surrounding tissue, leading to the formation of pus and abscesses.
Mitochondrial dysfunction: Mitochondrial dysfunction refers to the impaired ability of mitochondria to perform their essential functions, such as energy production, regulation of metabolism, and apoptosis. This dysfunction can lead to a variety of cellular problems, contributing to either apoptosis or necrosis, depending on the severity and context of the impairment. Understanding mitochondrial dysfunction is crucial as it plays a significant role in various diseases and conditions, impacting cellular health and death mechanisms.
Necrosis: Necrosis is the process of uncontrolled cell death caused by factors such as infection, injury, or lack of blood flow. This type of cell death often leads to inflammation and can affect surrounding tissues, making it a key concept in understanding how cells respond to various stresses and injuries.
Phagocytosis: Phagocytosis is a cellular process where specialized cells, known as phagocytes, engulf and digest foreign particles, bacteria, and dead or dying cells. This mechanism is crucial for maintaining homeostasis and protecting the body against infections. Phagocytosis plays a significant role in both innate and adaptive immunity, serving as an essential function in clearing pathogens and cellular debris from the body.
Programmed Cell Death: Programmed cell death, often referred to as apoptosis, is a controlled process by which cells undergo a systematic and regulated self-destruction. This mechanism is crucial for maintaining cellular homeostasis, development, and tissue remodeling, and it differentiates from necrosis, which is an uncontrolled form of cell death typically resulting from injury or disease. Understanding programmed cell death helps in recognizing its role in various physiological and pathological conditions, including cancer and neurodegenerative disorders.
Tissue remodeling: Tissue remodeling is a dynamic process involving the structural and functional alterations of tissues in response to various stimuli, including injury and repair. This process is crucial for restoring tissue integrity and function following cell death, whether it results from apoptosis or necrosis. Tissue remodeling helps to reorganize extracellular matrix components and facilitate the adaptation of tissues to new conditions or stresses.
Troponin: Troponin is a complex of three proteins found in cardiac and skeletal muscle, playing a crucial role in muscle contraction regulation. It consists of troponin C, troponin I, and troponin T, each serving distinct functions in response to calcium ions. Elevated levels of troponin in the bloodstream are often indicative of myocardial injury, particularly in the context of heart attacks, making it an important biomarker in clinical settings.