Apoptosis: Oxidative Stress and Antioxidants

Reactive oxygen species (ROS) are fundamental to apoptosis, the programmed cell death essential for multicellular organisms’ survival and proper functioning. ROS production within cells is meticulously balanced by various antioxidant defenses. At physiological levels, ROS are vital for regulating cell cycle progression, proliferation, differentiation, migration, and apoptosis. Additionally, they play crucial roles in maintaining redox homeostasis, bolstering immune function, and activating diverse cellular signaling pathways. However, excessive ROS can cause significant damage to proteins, nucleic acids, lipids, membranes, and organelles, thereby triggering cell death mechanisms like apoptosis. Apoptosis consists of three distinct phases: induction, effector, and execution, each significantly influenced by ROS and oxidative stress. Mitochondrial dysfunction is a pivotal event in apoptosis, leading to the release of apoptotic factors such as cytochrome C, apoptosis-inducing factor (AIF), and apoptotic protease-activating factor-1 (APAF-1), which activate caspases and result in cell death. This process is tightly regulated and is linked to various chronic diseases, including cancer, neurodegenerative disorders, and cardiovascular diseases. ROS-induced DNA damage, including mutations and gene rearrangements, can either prompt apoptosis or contribute to oncogenesis by affecting proto-oncogenes and tumor suppressor genes. Understanding the balance between ROS production and apoptosis regulation is critical for maintaining cellular homeostasis. ROS are central to cell signaling and regulate major apoptosis pathways mediated by mitochondria, death receptors, and the endoplasmic reticulum (ER). This review explores the role of ROS in these apoptosis pathways and examines the complex interactions between different ROS-mediated signaling mechanisms, highlighting areas of ongoing research in this field.