autophagy
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Classification
- macro-autophagy
- en-block engulfment of cytoplasm by smooth endoplasmic reticulum to form autophagosomes that fuse with lysosomes
- micro-autophagy
- direct engulfment of cytoplasmic contents by lysosome
- chaperone-mediated autophagy
- chaperone-mediated translocation of proteins & polynucleotides across the lysosomal membrane
* macro-autophagy is the major form of autophagy responding to environmental & physiologic signals
Function
- along with the 26S proteasome, one of two major degradation pathways[4]
- intracellular organelles & parts of cytoplasm are sequestered from the cytoplasm in an autophagic vacuole formed from ribosome- free regions of endoplasmic reticulum
- the vacuoles then fuse with primary lysosomes or Golgi to form autophagolysosomes
- 1 or more of at least 4 cysteine proteases (APG4A, APG4B, APG4C, APG4D) plus several other autophagy proteins are involved in conjugation of autophagy protein(s) including APG8L to phosphatidylethanolamine (PE) in the formation of autophagosomes
Autophagy occurs during:
- removal of damaged organelles during cell injury
- after infection, autophagy can eliminate invading intracellular bacteria & viruses[3]
- cellular remodeling of differentiation
- atrophy secondary to nutrient deprivation or hormonal involution
Pathology
- disrupted autophagy has been linked to Parkinson's disease, type 2 diabetes, cancer & other disorders in the elderly[3]
- mutations in autophagy genes can cause genetic disease[3]
Additional terms
References
- ↑ Cotran et al Robbins Pathologic Basis of Disease, 5th ed. W.B. Saunders Co, Philadelphia, PA 1994 pg 22
- ↑ UniProt http://www.uniprot.org/uniprot/Q9NT62.html
UniProt http://www.uniprot.org/uniprot/Q9Y4P1.html - ↑ 3.0 3.1 3.2 3.3 The Nobel Assembly at Karolinska Institutet The Nobel Prize in Physiology or Medicine 2016. Yoshinori Ohsumi Press Release: Oct 3, 2016 http://www.nobelprize.org/nobel_prizes/medicine/laureates/2016/press.html
- ↑ 4.0 4.1 Mizushima N, Levine B. Autophagy in Human Diseases. N Engl J Med 2020; 383:1564-1576 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33053285 https://www.nejm.org/doi/10.1056/NEJMra2022774