Cell death might sound a bit "scary," but it's actually a perfectly normal part of life! Today, let's dive into the fascinating world of necroptosis and uncover the secrets behind this unique form of cell death.
Necroptosis is a form of programmed cell death that lies between apoptosis (cellular suicide) and necrosis (accidental cell death). It combines the programmed characteristics of apoptosis with the inflamm
atory response of necrosis. In simple terms, it's like a "hybrid" of cell death, with both "elegant" and "intense" aspects.
The occurrence of necroptosis relies on a series of complex signaling pathways. Among them, RIPK1 (Receptor-Interacting Protein Kinase 1) and RIPK3 (Receptor-Interacting Protein Kinase 3) are the key "switches." When cells are exposed to certain stimuli, RIPK1 and RIPK3 become activated. They interact with each other to form a complex, which then activates MLKL (Mixed Lineage Kinase Domain-Like protein). Once activated, MLKL translocates to the cell membrane, forming pores that increase membrane permeability, leading to the leakage of cellular contents and ultimately causing necroptosis.
Recently, scientists have discovered a new mechanism: MLKL polymerization induces lysosomal membrane permeabilization (MPI-LMP), which in turn promotes necroptosis. In this process, cathepsin B (CTSB) plays a crucial role. It's as if the cell's internal "defenses" are breached, causing cellular contents to "leak" and ultimately leading to cell death.
Necroptosis plays an important role in both physiological and pathological processes. In physiology, it helps maintain tissue homeostasis by clearing damaged or infected cells and promoting tissue repair and regeneration. For example, during embryonic development, it helps remove excess cells to refine tissue structure and function.
In pathology, necroptosis is closely related to various diseases. For instance, in ischemia-reperfusion injury, when blood supply is restored, cells are subjected to oxidative stress and calcium overload, which activate necroptosis pathways, leading to massive cell death and worsening tissue damage. Additionally, necroptosis is implicated in the development and progression of neurodegenerative diseases, autoimmune diseases, and cancer.
Scientists have been exploring the mysteries of necroptosis in the hope of finding ways to intervene and provide new therapeutic strategies for diseases. Recent studies have shown that inhibiting the activity of RIPK1 or RIPK3 can reduce necroptosis, thereby alleviating tissue damage. Other research has found that the PUMA–RIPK3-necroptosis axis can trigger immunogenic antitumor responses, enhancing the efficacy of certain drugs.
These studies not only deepen our understanding of necroptosis but also bring new hope for future disease treatments. Perhaps one day, we will be able to precisely regulate necroptosis to treat some of the currently intractable diseases!
Reference: Bertheloot, D., Latz, E. & Franklin, B.S. Necroptosis, pyroptosis and apoptosis: an intricate game of cell death. Cell Mol Immunol 18, 1106–1121 (2021).
Voisey
Voisey is a technical support specialist at EnkiLife, proficient in immunology and cell biology. She is committed to providing customers with professional and efficient technical support. Additionally, she is involved in research on customers' fields of study and designs highly cost-effective solutions for them.
