Abstract:
"The term ‘Autophagy’ coined by Christian de Duve in 1963 derives its origin from the
Greek words ‘auto’ and ‘phagy’ which literally translates to self-eating [1].
Macroautophagy (herein autophagy) is a cellular degradation pathway in which
cytoplasmic components are captured in double membrane vesicles called
‘autophagosomes’ and delivered to lysosomes for degradation. The process of
autophagy is evolutionarily conserved from yeast to mammals and has an indispensable
role in maintaining cellular homeostasis. Around 38 autophagy related genes (ATGs)
have been identified in Saccharomyces cerevisiae and Pichia pastoris and many of
them are functionally conserved in higher eukaryotes [2]. Autophagy occurs at a basal
rate in cells during normal growth conditions and is involved in degradation and
removal of damaged or dead organelles and misfolded proteins [3]. The difference in
levels of basal autophagy among different tissues was shown using transgenic mice
expressing a fluorescent autophagosome marker. Basal autophagy levels were ranging
from extremely low in brain, moderate in pancreatic acinar cells and relatively high in
thymic epithelial cells [4]. Depending on how the cargo is sequestered, autophagy is of
three types: Macroautophagy, microautophagy and chaperone mediated autophagy
(CMA). Macroautophagy is the main autophagy pathway, in which cargo is sequestered
in double membrane autophagosomes and taken to lysosomes. In microautophagy, the
part of cytoplasm which needs to be degraded is directly engulfed in lysosome by
invagination and folding of lysosomal membrane. In chaperone mediated autophagy
(CMA), the protein cargo is recognised by the chaperone Hsc-70 which interacts with
lysosomal membrane protein LAMP2A, unfolds the substrate protein, and transfers it
across lysosomal membrane for degradation. Depending on the presence and absence
of selectivity factors, autophagy is of two types: general and selective autophagy. Bulk
degradation of long lived proteins and cytoplasmic components is called general
autophagy. Selective autophagy involves specific recognition of cargo by autophagy
receptors like p62, NBR1, Optineurin etc and their subsequent loading in
autophagosomes [5]."
