Autophagy: Fasting at Cellular Level

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Life on earth is sustained primarily by flow of energy. Living organisms obtain this energy in multiple ways; plants photosynthesize their food, whereas animals feed on other organisms and indirectly harness energy. At the cellular level energy requirement is met by catabolic processes which act on complex substrates to yield ATP the cellular energy currency.

What is fasting?

Fasting is a popular concept across diverse cultures. It is indicated as a practice to detoxify the body.  It involves willful abstinence from food and water for a defined period of time. During a fast the body makes use of stored form of energy i.e., glycogen to fuel the system which enables us to carry on daily activities. What happens once the body runs out of the stored fuel glycogen? Cells have evolved a clever mechanism to combat such situation called as autophagy.

Discovery of autophagy: self-eating

Autophagy literally means self-eating. It was first described by Nobel laureate Christian de Duve who observed membranous vesicles in the cells engulfing cytoplasmic contents fusing with the lysosome, an organelle in the cell that is rich in digestive enzymes. This results into degradation of the vesicle contents, which is recycled by cells and used as resource. Thus, autophagy is the mechanism, which comes to our rescue under starvation situation and is found to be evolutionary conserved across eukaryotic life forms.

The cell biologist Y. Oshumi revealed the molecular mechanism of autophagy using Baker’s yeast as a model organism and was awarded Nobel prize in 2016. He grew mutant yeast cells lacking a number of genes associated with survival during nutrient. Those genes turned out to be the autophagy genes, and there are approximately 30 such genes.

Autophagy: multifunctional pathway

Autophagy involves packaging of the cargo in vesicles called autophagosomes, which fuse with the lysosome to deliver the cargo. On the basis of selection of the substrate to be degraded, autophagy is classified as selective and non selective autophagy. Damaged or nonfunctional organelles are also the target of autophagy. For example, mitophagy involves removal of damaged mitochondria, likewise ribophagy is for ribosomes and pexophagy for peroxisomes. Recent studies throw light on how cells use autophagy to combat infections wherein pathogens are engulfed and targeted for lysosomal degradation, this is known as xenophagy. Differences in the mechanism of autophagy between host and pathogens are an upcoming target of novel drugs to fight disease. Mutation in autophagy genes are known to cause neurodegenerative diseases.

Thus, autophagy, which was in the beginning thought to be a mere process to survive during nutritional deprivation, is emerging to contribute towards health and longevity.

Authors: Renu Sudhakar, Deepak Kumar and Puran Singh Sijwali, CSIR-Centre for Cellular and Molecular Biology. 

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