The word autophagy is derived from Greek words “auto” meaning self and “phagy” meaning eating. Autophagy is a normal physiological process in the body that deals with destruction of cells in the body.

It maintains homeostasis or normal functioning by protein degradation and turnover of the destroyed cell organelles for new cell formation.

During cellular stress the process of Autophagy is upscaled and increased. Cellular stress is caused when there is deprivation of nutrients and/or growth factors.

Thus Autophagy may provide an alternate source of intracellular building blocks and substrates that may generate energy to enable continuous cell survival.

Autophagy and cell death: Autophagy also kills the cells under certain conditions. These are form of programmed cell death (PCD) and are called autophagic cell death. Programmed cell death is commonly termed apoptosis.

Autophagy is termed a nonapoptotic programmed cell death with different pathways and mediators from apoptosis.

Autophagy mainly maintains a balance between manufacture of cellular components and break down of damaged or unnecessary organelles and other cellular constituents. There are some major degradative pathways that include proteasome that involves breaking down of most short-lived proteins.

Autophagy and stress: Autophagy enables cells to survive stress from the external environment like nutrient deprivation and also allows them to withstand internal stresses like accumulation of damaged organelles and pathogen or infective organism invasion.

Autophagy is seen in all eukaryotic systems including fungi, plants, slime mold, nematodes, fruit flies and insects, rodents (laboratory mice and rats), humans.

Types of autophagy:

There are several types of Autophagy. These are:-

  • Microautophagy – in this process the cytosolic components are directly taken up by the lysosome itself through the lysosomal membrane.
  • Macroautophagy – this involves delivery of cytoplasmic cargo to the lysosome through the intermediary of a double membrane-bound vesicle. This is called an autophagosome that fuses with the lysosome to form an autolysosome.
  • Chaperone-mediated autophagy – in this process the targeted proteins are translocated across the lysosomal membrane in a complex with chaperone proteins (such as Hsc-70).  
  • Micro- and macropexophagy
  • Piecemeal microautophagy of the nucleus
  • Cytoplasm-to-vacuole targeting (Cvt) pathway

Macro-autophagy: This method uses a double membrane-bound vesicle to deliver the cytoplasmic cargo to the lysosome. This double membrane-bound vesicle is called autolysosome, and it fuses with the lysosome.

Micro-autophagy: In this method, the components of cytoplasm are directly taken by the lysosome by invagination of the lysosomal membrane. In both macro- and micro-autophagy, large structures can be engulfed using specific and non-specific mechanisms.

Chaperone-mediated autophagy: In this method, the targeted proteins form a complex with chaperone proteins and then translocate across the lysosomal membrane. This complex is then recognized by lysosomal membrane receptor lysosomal-associated membrane protein 2A, leading to unfolding the degradation of the complex.

Signaling pathways involved in autophagy: Rapamycin kinase (TOR kinase) acts as a signaling control point downstream of growth factor, hypoxia, ATP, and insulin signaling pathways. Akt kinase, PI3-kinase and growth factor receptors can activate TOR kinase when the nutrients are available, and this can promote growth and protein translation.

Hypoxia can also activate autophagy, by either hypoxia-inducable factor (HIF) pathway or HIF independent pathways. Thus, selective autophagy can help in eliminating ER and mitochondria when sufficient oxygen is not available.

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