Contact Us | Register | Login

Pharmacology All Targets 7-TM Receptors Ion Channels Nuclear Receptors Enzyme-Linked Receptors Transporters Enzymes Other Pharmacology Cellular Processes Angiogenesis Apoptosis Cell Cycle Cell Metabolism Cytoskeleton & Motor Proteins ECM & Adhesion Molecules Epigenetics Signal Transduction Stem Cells Signaling Pathways Product Type All Products New Products Small Molecules Peptides Controlled Substances Toxins Caged Compounds Fluorescent Probes Screening Libraries Ligand Sets Other Product Types Research Area Cancer Cardiovascular System Endocrinology Immunology Neuroscience Pain & Inflammation Respiratory System

Autophagy

Supporting information

Autophagy is a process by which a cell breaks down macromolecules in response to starvation or stress signals. While it is closely linked with apoptosis, autophagy is primarily characterized as a catabolic mechanism by which cellular energy homeostasis is maintained, and by which cellular organelles and proteins are degraded.

Autophagy also occurs in response to similar stresses as those which induce apoptosis and several proapoptotic signals also induce autophagy - for example, TRAIL, ceramide and the DAPk (death-associated protein kinase) family. However, the way in which the cell is degraded differs: autophagy makes use of the cell's integral lysosomal machinery; apoptosis instead makes use of phagocytic cell lysosomes. These two mechanisms are characteristic of each process and help distinguish them under the microscope.

By enabling the degradation of organelles and macromolecules, autophagy helps provide cells with nutrients under starvation conditions. It assists in the removal of damaged mitochondria and proteins too large to be degraded by the ubiquitin-proteasomal system, as well as helping to maintain whole body homeostasis by removing irreversibly damaged cells. Under conditions such as infection and protein aggregation, this capacity to break down cellular components may also aid cell survival and alleviate neurodegeneration. Compromised autophagy can result in the aggregation of tau, α-synuclein and mutant huntingtin protein fragments, all of which are autophagy substrates and which are linked to neurodegenerative disease. In addition, defective autophagy has been linked to metabolic disorders (such as diabetes and obesity) and aging. Autophagy has also been linked to cancer development - it helps maintain nutrient-deprived cells located in the center of tumors. Autophagy can be used as a target for combination therapies, in particular those which inhibit autophagy and promote apoptosis instead. The roles of autophagy in cancer are complex and often contrasting, and may vary during disease progression. As a result, the targeting of autophagy to treat cancer is more likely to be context-dependent, unlike other tumor processes such as cell growth, angiogenesis and apoptosis.

Intracellular control over autophagy is largely transduced by mTOR and PI 3-K signaling. mTORC1 is directly responsible for autophagy regulation and acts as an autophagy suppressor downstream of the class I PI 3-K-Akt pathway. Nutrient deprivation suppresses kinase activity, thus activating autophagy; AMPK activation inhibits mTOR-dependent signaling, therefore stimulating autophagy. mTOR-independent pathways involved in autophagy also exist, including calpain and inositol, but their mechanisms are yet to be fully elucidated.

View all products for Autophagy »

Literature for Autophagy

Cancer Research Guide

Autophagy Review

Autophagy Poster

© Copyright 2013 Tocris Bioscience. All Rights Reserved | Privacy and Cookie Policy | Site map