By Dr Ananya Mandal, MD
In a broad overview the functions of autophagy in the body can be outlined as:-
Housekeeping roles – these roles involve removal of aggregated and erroneously folded or formed proteins and removal and clearance of damaged organelles or cellular components. The damaged cell organelles include mitochondria from old and infirm cells and also the endoplasmic reticulum.
Host defence mechanism – autophagy helps kill cells that are infected or invaded by foreign pathogens. Thus it helps contain the infection and may act as part of the immunity of the cellular organism.
Role in cellular stress – autophagy is a response to cellular stress. It regulates the processes that occur when there is nutrient deprivation and cellular stress.
Embryonic development – autophagy plays an important role in development of the embryo by maintain a critical balance of energy levels and sources.
Autophagy and cellular survival
Autophagy plays an important role in the survival of cellular organisms. When there is starvation or nutrient deprivation, the process of autophagy is triggered. This gives rise to formation of double membrane autophagic vacuoles, also known as autophagosomes that transport the cargo from the cytoplasm to the lysosome for degradation.
Regulation of autophagy is genetically linked. These genes are thought to be linked with other fundamental cellular processes as well.
Growth involves a balance between anabolic and catabolic processes such as protein synthesis and degradation. This means cellular degradation and formation are also part of the balance of growth.
Autophagy and cell death
There is an association between cell death and autophagy. There is also a link between programmed cell death like apoptosis and autophagy.
Cells exposed to extracellular ligands signalling death including tumour-necrosis factor (TNF) and Fas ligand, undergo apoptosis or cell death.
Several of these ligands as well as caspases are involved in apoptosis. Caspase-8 and caspase-10 may directly activate effecter caspases such as caspase-3, or activate the mitochondrial apoptosis pathway.
There are several caspase-independent pathways of apoptosis as well. Studies have shown that inhibition of caspase-8 induced cell death lead to formation autophagic vacuoles in these cells.
Similarly in salivary gland cells when caspases are activated, only then autophagic vacuoles are seen. This links autophagy to cell death and apoptosis. This also indicates that autophagy might be involved in degrading cell structures after death related proteases are activated.
Reviewed by April Cashin-Garbutt, BA Hons (Cantab)