DSpace Repository

Insights into autophagic flux across three eukaryotic kingdoms

Show simple item record

dc.contributor.advisor Manjithaya, Ravi
dc.contributor.author Mishra, Piyush
dc.date.accessioned 2021-10-01T06:57:20Z
dc.date.available 2021-10-01T06:57:20Z
dc.date.issued 2017
dc.identifier.citation Mishra, Piyush. 2017, Insights into autophagic flux across three eukaryotic kingdoms, Ph.D thesis, Jawaharlal Nehru Centre for Advanced Scientific Research, Bengaluru en_US
dc.identifier.uri https://libjncir.jncasr.ac.in/xmlui/handle/123456789/3180
dc.description Open access en_US
dc.description.abstract Macroautophagy (herein autophagy) is a major intracellular pathway that is indispensable for maintaining cellular homeostasis. Autophagy has been reported in various organisms ranging from yeast to humans suggesting that it is an evolutionarily conserved process. This process was first reported by Christian de Duve (Deter et al., 1967). He identified this process of self-cannibalization which involves sequestration of cellular components within a double membranous structure called the autophagosome, which then fuses with the lysosomes and releases the cargo into it for degradation. The degradation products, like amino acids are recycled back to the cytoplasm and are used up by the cell (Klionsky, 2007; Rabinowitz & White, 2010). This entire phenomenon of cargo capture and ultimately its degradation in the lysosomes is called ‘autophagic flux’. Basal levels of autophagy occur in all cells during nutrient rich conditions and help in housekeeping functions (Mizushima et al., 2004; Musiwaro et al., 2013). However, levels of autophagy dramatically increase via extracellular or intracellular stimulation such as starvation, pathogen invasion, organelle damage and protein aggregation in cytoplasm. Thus autophagy can serve as an adaptive response to provide energy and nutrients to the cell during starvation conditions (Takeshige et al., 1992; Tsukada & Ohsumi, 1993) and also get rid of aggregated proteins, unnecessary or damaged organelles and intracellular pathogens (xenophagy) to act as a cellular rubbish disposal mechanism. Because autophagy is central to maintaining cellular homeostasis, dysfunctional autophagy has been attributed to a variety of disease conditions such as cardiovascular diseases, atherosclerosis, certain myopathies, innate and adaptive immune responses and cancer (Kroemer, 2015). Autophagy also serves a neuroprotective role, as it clears large aggregates of proteins that are resistant to proteasomal degradation. Aim and scope of the study Although the core autophagy machinery and the proteins involved in disease conditions might be known, but the exact mechanism of action and how the autophagic flux is regulated is not completely understood which leads to many unanswered questions. Understanding and controlling the autophagic flux either through a genetic or pharmacological approach is a highly promising approach and of great scientific interest. Studies with genetic modulations of autophagic flux have been carried out in the past with immense success. Yoshinori Ohsumi was awarded the Nobel Prize in 2016 as a pioneer in the field and his contribution to the study of autophagic flux. In the present study however, we used the pharmacological approach as a means to study autophagy. Chemical modulation has an advantage over genetic manipulations that the phenotype could be observed just on the addition of the compound and the action could be reversed on its withdrawal. The method is less laborious and the putative modulators could be used as leads for pharmacological purposes in certain disease conditions. en_US
dc.language English en
dc.language.iso en en_US
dc.publisher Jawaharlal Nehru Centre for Advanced Scientific Research en_US
dc.rights JNCASR theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. en
dc.subject Autophagy en_US
dc.subject Pathology en_US
dc.title Insights into autophagic flux across three eukaryotic kingdoms en_US
dc.type Thesis en_US
dc.type.qualificationlevel Doctoral en_US
dc.type.qualificationname PhD en_US
dc.publisher.department MBGU en_US


Files in this item

This item appears in the following Collection(s)

Show simple item record

Search DSpace


Advanced Search

Browse

My Account