Autophagy

The term autophagy means “self-eating”, and under normal conditions it is simply a maintenance- and recycling-system, where used or damaged intracellular organelles and molecules are digested by the cell and used in de-novo synthetic pathways or for energy-production. Autophagy is often up-regulated in the early stages of pathology, while at later stages it might be repressed, however, this is poorly studied. The primary reason for increased activation is cellular nutrient-starvation, which can occur as a consequence of insufficient dietary intake, inflammation, infection or a combination of any of these three. In the normal physiological state cells take in energy from the periphery in the form of amino acids, sugars and lipids supplied from the bloodstream, but in the case of injury and subsequent inflammation which create a temporary break in nutrient supply, or under an infectious threat where the cells energy-producing mechanisms and anabolic pathways may fall under parasitic influence, the cell instead switch to a phagocytic-like phenotype. The intracellular environment then starts to resemble the physiology of a stomach, and the cells begin to digest its own internal structure and also swallowing components of the extracellular matrix as well as invading pathogens. This creates a dormant and degenerative phenotype in the tissue, and in many ways autophagy resembles a state of hibernation, functioning as a protection-mechanism against harsh and harmful external conditions, a phenomenon that can be observed both at the level of the cell as well as in entire organisms. In general, the degree of host autophagic capacity is protective towards stressful cellular stimuli, but its persistent activation, which is common in disease is related to functional decline over time. The autophagic capacity of cells is seen also to decline with advancing age and level of disease.

Supporting Evidence

• The extracellular matrix are used as an energy-source in starved epithelial cells¹⁾https://www.nature.com/articles/ncomms13989
• Autophagy can be triggered by nutrient deprivation²⁾https://link.springer.com/article/10.1007/s10753-011-9311-y
• Autophagy can be used in infection to degrade intracellular bacteria, but may also be exploited by pathogens.³⁾https://www.frontiersin.org/articles/10.3389/fcell.2018.00147/full
• Stimulation with LPS causes chondrocytes and macrophages to degrade cartilage-tissue in vitro⁴⁾https://www.ncbi.nlm.nih.gov/pmc/articles/PMC437042/?page=1
• Sepsis leads to increased degradation of collagen type-I, perhaps as a cellular survival-mechanism⁵⁾http://jultika.oulu.fi/files/isbn9789514262548.pdf
• Some bacterial toxins enter cells by binding to glucose-transporters⁶⁾https://pubmed.ncbi.nlm.nih.gov/9421374/
• Hypometabolism in tissues are a strategy for disease-tollerance in infection⁷⁾ … Continue reading
• Injection of LPS into hibernating animals does not cause an immune-response⁸⁾https://www.ncbi.nlm.nih.gov/pubmed/11893609
• Autophagic ability antagonises apoptotic tendencies of cells in the short term.⁹⁾https://www.ncbi.nlm.nih.gov/pubmed/28232016
• Persistent activation of autophagy causes apoptosis.¹⁰⁾https://sci-hub.tw/https://www.ncbi.nlm.nih.gov/pubmed/28232016
• Cellular glucose-starvation causes up-regulated autophagy.¹¹⁾https://link.springer.com/article/10.1186/2049-3002-2-2
• Cold-exposure causes up-regulation of autophagy in muscle.¹²⁾https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5045934/

Association with Disease

• Autophagy is enhanced in early OA, while decrease autophagic function is related to faster decline.¹³⁾https://www.sciencedirect.com/science/article/pii/S1297319X15001608¹⁴⁾https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5187946/
• Enhanced autophagic activity in synovial cells from RA-patients might explain resistance to apoptosis.¹⁵⁾https://link.springer.com/article/10.1007/s00011-012-0572-1
• Increased autophagic activity of tenocytes in TP.¹⁶⁾https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5449348/
• Evidence for enhanced autophagic activity in DDD.¹⁷⁾https://www.ncbi.nlm.nih.gov/pubmed/26091153¹⁸⁾https://onlinelibrary.wiley.com/doi/pdf/10.1111/os.12573
• Altered autophagy in different cell-types is associated with AS and plaque-instability.¹⁹⁾https://www.ncbi.nlm.nih.gov/pubmed/30318118²⁰⁾https://journal-inflammation.biomedcentral.com/articles/10.1186/s12950-019-0212-4