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.

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Literature for Autophagy

Cancer Research Product Guide

A collection of over 750 products for cancer research, the guide includes research tools for the study of:

  • Cancer Metabolism
  • Epigenetics in Cancer
  • Receptor Signaling
  • Cell Cycle and DNA Damage Repair
  • Angiogenesis
  • Invasion and Metastasis
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Cancer Research Product Guide
Neurodegeneration Product Guide

A collection of over 275 products for neurodegeneration research, the guide includes research tools for the study of:

  • Alzheimer's disease
  • Parkinson's disease
  • Huntington's disease
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Neurodegeneration Product Guide
Autophagy Scientific Review

This review summarizes the molecular mechanisms, physiology and pathology of autophagy. The role of autophagy in cell death and its links to disease are also discussed. Compounds available from Tocris are listed.

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Autophagy Scientific Review
Autophagy Life Science Poster

Autophagy is a cellular process used by cells for degradation and recycling. Written by Patricia Boya and Patrice Codogno, this poster summarizes the molecular machinery, physio Request copy | Download PDF | View all posters

Autophagy Life Science Poster
Programmed Cell Death Life Science Poster

Written by Bram van Raam & Guy Salvesen, this poster summarizes the signaling pathways involved in apoptosis, necroptosis and cell survival following death receptor activation, and highlights the influence of the molecular switch, cFLIP, on cell fate.

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Programmed Cell Death Life Science Poster

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Cancer Research Product Guide

Cancer Research Product Guide

Our Cancer Research Guide highlights over 750 products for cancer research. Request copy or view PDF today.

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Neurodegeneration Research Product Guide

Neurodegeneration Product Guide

Our Neurodegeneration guide highlights over 275 products for neurodegeneration research. Request copy or view PDF today.

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Autophagy Review

Written by P. Boya & P. Codogno

Autophagy Scientific Review

Our Autophagy review summarizes the molecular mechanisms and physiology of autophagy, as well as the role of autophagy in certain disease states. Request copy or view PDF today.

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Autophagy: Mechanisms and Function

Written by Patricia Boya and Patrice Codogno

Autophagy Life Science Poster

Our Autophagy poster summarizes the molecular machinery, physiology and pathology of autophagy, and highlights chemical compounds that modulate autophagy. Request copy or view PDF today.

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Programmed Cell Death

Written by Bram van Raam and Guy Salvesen

Programmed Cell Death Life Science Poster

Our Programmed Cell Death poster gives a summary of the signaling pathways involved in apoptosis, necroptosis and cell survival. Request copy or view PDF today.

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Epigenetic Regulation of Stem Cell Differentiation

March 1, 2017

Amsterdam, The Netherlands