Apoptosis: ER Stress and Disease Pathology

Multicellular creatures depend on the carefully controlled process of apoptosis, often known as programmed cell death. Through this technique, organisms can get rid of cells that are redundant or even hazardous, including ones that contain mutations or are infested with viruses. Apoptotic cells experience a series of morphological and metabolic alterations as part of a cascade of self-destruction. Cellular homeostasis requires effective control over the programmed cell death process. A crucial quality-control organelle for protein homeostasis, or “proteostasis,” is the endoplasmic reticulum (ER). This encompasses multiple processes of protein quality control, including autophagy, protein chaperones, and ER-associated degradation. ER stress is brought on by a build-up of misfolded or unfolded proteins that disrupt proteostasis. An adaptive unfolded protein response (UPR) is triggered to maintain proteostasis. The activation of inositol-requiring enzyme 1 (IRE1), activating transcription factor 6 (ATF6), and protein kinase R-like ER kinase (PERK) are all involved in this reaction. Transcription and protein processing are just two of the many epigenetic factors that are impacted by ER stress. Elevated levels of cellular stress can cause harm to lipids, proteins, nucleic acids, membranes, and organelles, which may initiate processes leading to cell death, including apoptosis. Reactive oxygen species (erROS) formed from the endoplasmic reticulum (ER) are also essential for controlling major apoptosis pathways and cell signaling. The ER, death receptors, and mitochondria control these pathways. With an emphasis on metabolic, inflammatory, and neoplastic disorders, this book chapter explores the current understanding of ER stress’s role in the principal apoptotic pathways associated with various human diseases. It draws attention to the complex interactions and feedback loops that exist between these signaling pathways and how they relate to apoptosis, underscoring the need for more study to understand these relationships fully.