Regulation of Apoptotic Mitochondrial Events

Cell Death: Apoptosis and Necrosis

• Cell death is a fundamental process of life, playing a crucial role in embryonic development, maintaining homeostasis, and eliminating damaged cells.

Apoptosis

• Apoptosis is a type of programmed cell death (PCD), driven by tightly regulated intracellular signal transduction pathways.
• It occurs under normal physiological conditions, and the cell is an active participant in its own demise ("cellular suicide").
• Apoptosis involves a series of tightly controlled events, characterized by cell shrinkage, membrane blebbing, positional organelle loss, DNA condensation, and fragmentation.

Physiological Conditions of Apoptosis

• Apoptosis plays a beneficial and important role in embryonic development, tissue homeostasis, and the elimination of damaged cells.
• In embryonic development, apoptosis helps in digit formation, and lack of apoptosis can lead to webbed fingers (syndactyly).
• In adults, apoptosis is involved in normal cell turnover, tissue homeostasis, immune tolerance, and the elimination of activated, damaged, and abnormal cells.

Apoptosis Pathways

• There are two main pathways: the extrinsic pathway (death receptor-mediated events) and the intrinsic pathway (mitochondria-mediated events).
• The extrinsic pathway involves death receptors, such as FasR and TNFR1, which have a cytoplasmic domain called the "death domain".
• The intrinsic pathway involves changes in the mitochondrial outer membrane, leading to the release of pro-apoptotic proteins and the activation of caspases.

Caspases

• Caspases are a family of intracellular cysteine proteases that play a pivotal role in the initiation and execution of apoptosis.
• There are at least 14 different members of caspases in mammalian cells, which can be broadly categorized into signaling or initiator caspases, effector or executioner caspases, and inflammatory caspases.

Necrosis

• Necrosis is a type of non-programmed cell death, resulting from accidental cell injury or environmental factors.
• Necrosis occurs due to physical or chemical insults, such as radiation, hypoxia, hyperthermia, and ischemia.
• The enzymes that digest the necrotic cell are derived from the lysosomes of the dying cells themselves and from the lysosomes of leukocytes that are called in as part of the inflammatory reaction.

Morphological and Biochemical Differences between Necrosis and Apoptosis

• Necrotic cells exhibit volume enlargement, swelling of cytoplasm and mitochondria, and loss of membrane integrity.
• Apoptotic cells exhibit volume reduction, shrinking of cytoplasm, and formation of apoptotic bodies.
• Apoptotic cells also show condensation of chromatin and DNA fragmentation, whereas necrotic cells do not.
• The main difference between apoptosis and necrosis is the way cells die, with apoptosis being a controlled and regulated process, and necrosis being an uncontrolled and accidental process.