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In cell biology, autophagy, or autophagocytosis, is a catabolic process involving the degradation of a cell's own components through the lysosomal machinery. It is a tightly regulated process which plays a normal part in cell growth, development, and homeostasis, where it helps maintain a balance between the synthesis, degradation, and subsequent recycling of cellular products. It is a major mechanism by which a starving cell reallocates nutrients from unnecessary processes to more essential processes.

A variety of autophagic processes exist, all sharing in common the degradation of intracellular components via the lysosome. The most well known mechanism of autophagy involves the formation of a membrane around a targeted region of the cell, separating the contents from the rest of the cytoplasm. The resultant vesicle then fuses with a lysosome and subsequently degrades the contents.

It was first described in the 1960s[1], but many questions still remain to be elucidated about the actual processes and mechanisms involved. Its role in disease is not well categorised, it may help to halt the progression of some diseases and plays a protective role against infection by intracellular pathogens; however, in some situations it may actually contribute to the development of a disease.



Autophagy is derived from Greek roots: auto - self, and phagy - eating. While the use of Greek roots may be correct in using these two terms as synonyms, each is applied to different areas of study and should not be used interchangeably. One of the most exciting finds was a previously unknown gene common to type 1 diabetes and Crohn's disease, a type of inflammatory bowel disorder, suggesting that they share similar biological pathways. The team also unexpectedly found a process known as autophagy - a process of clearing bacteria from within cells - is important in the development of Crohn's disease


  Autophagy can be broadly separated into three types: macroautophagy, microautophagy and chaperone-mediated autophagy. Macroautophagy involves the formation of a de-novo formed membrane sealing on itself to engulf cytsolic components (proteins and/or whole organelles)which are degraded after its fusion with the the lysosome while microautophagy is the direct invagination of materials into the lysosome. Specific types of autophagy include:

  • Chaperone-mediated autophagy, a term used to describe the degradation of specific cytosolic proteins marked with a specific peptide sequence. Chaperone molecules bind to and transport marked proteins to the lysosome via a receptor complex.
  • Pexophagy, autophagy selective for degradation of peroxisomes, which can be separated into macropexophagy and micropexophagy.
  • Mitophagy, autophagy selective for degradation of mitochondria is called, which can be separated in macromitophagy and micromitophagy.
  • Xenophagy, autophagy selective for degradation of intracellular bacteria and viruses.


Macroautophagy is the sequestration of organelles and long-lived proteins in a double-membrane vesicle, called an autophagosome or autophagic vacuole (AV), inside the cell. Autophagosomes form from the elongation of small membrane structures known as autophagosome precursors. The outer membrane of the autophagosome fuses in the cytoplasm with a lysosome to form an autolysosome or autophagolysosome where their contents are degraded via acidic lysosomal hydrolases.[2]

Microautophagy, on the other hand, happens when lysosomes directly engulf cytoplasm by invaginating, protrusion, and/or septation of the lysosomal limiting membrane.

In Chaperone-mediated autophagy or CMA only those proteins which have a consensus peptide sequence get recognized by the binding of a hsc70-containing chaperone/co-chaperone complex. This CMA substrate/chaperone complex then moves to the lysosomes where the CMA receptor lysosome-associated membrane protein type-2A (LAMP-2A) recognizes it, the protein is unfolded and translocated across the lysosome membrane assisted by the lysosomal hsc70 on the other side. CMA differs from macroautophagy and microautophagy in two main ways. (i) The substrates are translocated across the lysosome membrane on a one-by-one basis whereas in the macroautophagy and microautophagy the substrates are engulfed or sequestered in-bulk. (ii) CMA is very selective in what it degrades and can only degrade certain proteins and not organelles.

Autophagy is part of everyday normal cell growth and development where mTOR plays an important regulatory role.


Nutrient starvation

During nutrient starvation increased levels of autophagy lead to the breakdown of non-vital components and the release of nutrients, ensuring that vital processes can continue[3]. Mutant yeast cells which have a reduced autophagic capability rapidly perish in nutrition-deficient conditions[4]. A gene known as Atg7 has been implicated in nutrient-mediated autophagy, as mice studies have shown that starvation-induced autophagy was impaired in Atg7-deficient mice[5].


Autophagy plays a role in the destruction of some bacteria within the cell. Intracellular pathogens such as Mycobacterium tuberculosis persist within cells and block the normal actions taken by the cell to rid itself of it. Stimulating autophagy in infected cells overcomes the block and helps to rid the cell of pathogens[6].

Programmed cell death

It has been proposed that autophagy resulting in the total destruction of the cell is one of several types of programmed cell death, though no conclusive evidence exists for such a process[7]. Nevertheless, observations that cells possessing autophagic features in areas undergoing programmed cell death have led to the coining of the phrase autophagic cell death (also known as cytoplasmic cell death or type II cell death). Studies of the metamorphosis of insects have shown cells undergoing a form of programmed cell death which appears distinct from other forms, these have been proposed as examples of autophagic cell death[8].

It is not known if autophagic activity in dying cells actually causes death or if it simply occurs as a process alongside it. In many neurological diseases, certain neuronal cell death pathways and after neuronal injury there are increased numbers of autophagosomes. A causative relationship between autophagy and cell death has not been established. It is unclear if the increase in autophagosomes indicates an increase in autophagic activity or decreased autophagosome-lysosome fusion.[2] Recently it has been argued that autophagy might actually be a survival mechanism on behalf of the cell[7].

See also


  1. ^ Stromhaug PE, Klionsky DJ (2001). "Approaching the Molecular Mechanism of Autophagy". Traffic 2 (8).
  2. ^ a b Rubinsztein DC et al. (2005) Autophagy and Its Possible Roles in Nervous System Diseases, Damage and Repair. Autophagy 1(1):11-22. PMID 16874055
  3. ^ Yorimitsu T, Klionsky DJ (2005). "Autophagy: molecular machinery for self-eating". Cell Death and Differentiation (2005) 12, 1542–1552 12.
  4. ^ Tsukada M, Ohsumi Y (1993). "Isolation and characterization of autophagy-defective mutants of Saccharomyces cerevisiae.". FEBS Lett. 333.
  5. ^ M Komatsu et al. (2005). "Impairment of starvation-induced and constitutive autophagy in Atg7-deficient mice". JCB 169 (3).
  6. ^ Gutierrez MG et al. (2004). "Autophagy Is a Defense Mechanism Inhibiting BCG and Mycobacterium tuberculosis Survival in Infected Macrophages". Cell 119 (6).
  7. ^ a b Tsujimoto Y, Shimizu S (2005). "Another way to die: autophagic programmed cell death". Cell Death and Differentiation 12.
  8. ^ Schwartz LM, et al (1993). "Do All Programmed Cell Deaths Occur Via Apoptosis?". Proceedings of the National Academy of Sciences 90.
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Autophagy". A list of authors is available in Wikipedia.
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