{"id":{"repo_id":"the-open-u","oai_identifier":"oai:oro.open.ac.uk:55091"},"canonical_url":"https://search.dev.ndltd.org/etd/the-open-u/oai:oro.open.ac.uk:55091","repository":{"repo_id":"the-open-u","name":"The Open University","base_url":"https://oro.open.ac.uk/cgi/oai2"},"display":{"title":"The Role of Calcium Signalling in Autophagy","abstract":"Autophagy is a catabolic process that is important for degradation of cellular components, and for cell survival, and has also been associated with pathological disorders and tumour growth. Autophagy is a complex process; many factors and messengers converge to control steps along the autophagic pathway. Ca2+ has been proposed to regulate autophagy. However, Ca2+ has been proposed to be both pro- and anti-autophagic. To better understand how Ca2+ has these opposing effects, this study investigated in what ways particular sources of Ca2+, and the characteristics of Ca2+ signals impacted on autophagy.
The fundamental need for Ca2+ in the activation of autophagy was demonstrated by loading cells with an exogenous Ca2+ buffer, which prevented various stimuli from triggering autophagy.
Autophagy could be activated by inhibiting the transfer of Ca2+ from the endoplasmic reticulum to the mitochondrial matrix. This was achieved by expressing an enzyme that prevented Ca2+ release from inositol 1,4,5-trisphosphate receptors, inhibition of mitochondrial respiration, and knockdown of the mitochondrial Ca2+ uniporter. The triggering of autophagy under these conditions was due to reduced cellular ATP levels. These data suggest that Ca2+ signals arising from InsP3Rs suppress autophagy.
Additional studies used a well-characterised Ca2+ transport pathway to generate cellular Ca2+ signals, and examined their ability to trigger autophagy. This pathway, known as ‘store-operated Ca2+ entry’ (SOCE), was activated by depleting endoplasmic reticulum Ca2+ stores using inhibitors of sarco/endoplasmic reticulum ATPases (SERCA). It was found that sustained cellular Ca2+ signals arising via chronic inhibition of SERCA were pro-autophagic. The activation of autophagy absolutely required the presence of extracellular Ca2+, and was not due to cellular stress. Using pharmacological inhibition of various Ca2+-sensitive kinases, it was found that at least part of the autophagy that occurred during SOCE was due to activation of Ca2+/calmodulin-dependent kinase kinase-β (CaMKK-β, also known as CaMKK-2).","abstract_html":"Autophagy is a catabolic process that is important for degradation of cellular components, and for cell survival, and has also been associated with pathological disorders and tumour growth. Autophagy is a complex process; many factors and messengers converge to control steps along the autophagic pathway. Ca<sup>2+</sup> has been proposed to regulate autophagy. However, Ca<sup>2+</sup> has been proposed to be both pro- and anti-autophagic. To better understand how Ca<sup>2+</sup> has these opposing effects, this study investigated in what ways particular sources of Ca<sup>2+</sup>, and the characteristics of Ca<sup>2+</sup> signals impacted on autophagy. <br></br><br></br>The fundamental need for Ca<sup>2+</sup> in the activation of autophagy was demonstrated by loading cells with an exogenous Ca<sup>2+</sup> buffer, which prevented various stimuli from triggering autophagy. <br></br><br></br> Autophagy could be activated by inhibiting the transfer of Ca<sup>2+</sup> from the endoplasmic reticulum to the mitochondrial matrix. This was achieved by expressing an enzyme that prevented Ca<sup>2+</sup> release from inositol 1,4,5-trisphosphate receptors, inhibition of mitochondrial respiration, and knockdown of the mitochondrial Ca<sup>2+</sup> uniporter. The triggering of autophagy under these conditions was due to reduced cellular ATP levels. These data suggest that Ca<sup>2+</sup> signals arising from InsP<sub>3</sub>Rs suppress autophagy. <br></br><br></br> Additional studies used a well-characterised Ca<sup>2+</sup> transport pathway to generate cellular Ca<sup>2+</sup> signals, and examined their ability to trigger autophagy. This pathway, known as ‘store-operated Ca<sup>2+</sup> entry’ (SOCE), was activated by depleting endoplasmic reticulum Ca<sup>2+</sup> stores using inhibitors of sarco/endoplasmic reticulum ATPases (SERCA). It was found that sustained cellular Ca<sup>2+</sup> signals arising via chronic inhibition of SERCA were pro-autophagic. The activation of autophagy absolutely required the presence of extracellular Ca<sup>2+</sup>, and was not due to cellular stress. Using pharmacological inhibition of various Ca<sup>2+</sup>-sensitive kinases, it was found that at least part of the autophagy that occurred during SOCE was due to activation of Ca<sup>2+</sup>/calmodulin-dependent kinase kinase-β (CaMKK-β, also known as CaMKK-2).","abstract_has_math":false,"creators":["Chehab, Tala"],"institution":"The Open University","degree_name":"phd","degree_level":"doctoral","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2018,"date_issued":"2018-04","date_published":"2018-04","updated_at":"2026-07-24T05:02:52Z","subjects":[],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":null,"outbound_label":null,"outbound_source":null},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Chehab, Tala"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2018-04-13"]},{"key":"dc:date.issued","label":"Date","values":["2018-04"]},{"key":"dc:publisher.department","label":"Dc Publisher Department","values":["ARRAY(0x7ffb9a484548)"]},{"key":"dc:publisher.institution","label":"Dc Publisher Institution","values":["The Open University"]},{"key":"dc:relation.isreferencedby","label":"Dc Relation Isreferencedby","values":["https://oro.open.ac.uk/55091/"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"dc:type.qualificationlevel","label":"Dc Type Qualificationlevel","values":["doctoral"]},{"key":"dc:type.qualificationname","label":"Dc Type Qualificationname","values":["phd"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://oro.open.ac.uk/55091/1/__userdata_documents4_tc5664_Desktop_Tala%20Chehab-Thesis.pdf","https://oro.open.ac.uk/55091/8/Thesis%20Deposition%20Form.pdf","https://oro.open.ac.uk/55091/9/GRADPROG%20Memo.doc","https://oro.open.ac.uk/55091/16/Chehab%20-%20Library%20deposition%20memo.doc"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Autophagy is a catabolic process that is important for degradation of cellular components, and for cell survival, and has also been associated with pathological disorders and tumour growth. Autophagy is a complex process; many factors and messengers converge to control steps along the autophagic pathway. Ca2+ has been proposed to regulate autophagy. However, Ca2+ has been proposed to be both pro- and anti-autophagic. To better understand how Ca2+ has these opposing effects, this study investigated in what ways particular sources of Ca2+, and the characteristics of Ca2+ signals impacted on autophagy.
The fundamental need for Ca2+ in the activation of autophagy was demonstrated by loading cells with an exogenous Ca2+ buffer, which prevented various stimuli from triggering autophagy.
Autophagy could be activated by inhibiting the transfer of Ca2+ from the endoplasmic reticulum to the mitochondrial matrix. This was achieved by expressing an enzyme that prevented Ca2+ release from inositol 1,4,5-trisphosphate receptors, inhibition of mitochondrial respiration, and knockdown of the mitochondrial Ca2+ uniporter. The triggering of autophagy under these conditions was due to reduced cellular ATP levels. These data suggest that Ca2+ signals arising from InsP3Rs suppress autophagy.
Additional studies used a well-characterised Ca2+ transport pathway to generate cellular Ca2+ signals, and examined their ability to trigger autophagy. This pathway, known as ‘store-operated Ca2+ entry’ (SOCE), was activated by depleting endoplasmic reticulum Ca2+ stores using inhibitors of sarco/endoplasmic reticulum ATPases (SERCA). It was found that sustained cellular Ca2+ signals arising via chronic inhibition of SERCA were pro-autophagic. The activation of autophagy absolutely required the presence of extracellular Ca2+, and was not due to cellular stress. Using pharmacological inhibition of various Ca2+-sensitive kinases, it was found that at least part of the autophagy that occurred during SOCE was due to activation of Ca2+/calmodulin-dependent kinase kinase-β (CaMKK-β, also known as CaMKK-2)."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf","application/msword"]},{"key":"dc:title","label":"Title","values":["The Role of Calcium Signalling in Autophagy"]}]}],"canonical_facts":{"dc:creator":["Chehab, Tala"],"dc:date":["2018-04-13"],"dc:date.issued":["2018-04"],"dc:description.abstract":["Autophagy is a catabolic process that is important for degradation of cellular components, and for cell survival, and has also been associated with pathological disorders and tumour growth. Autophagy is a complex process; many factors and messengers converge to control steps along the autophagic pathway. Ca2+ has been proposed to regulate autophagy. However, Ca2+ has been proposed to be both pro- and anti-autophagic. To better understand how Ca2+ has these opposing effects, this study investigated in what ways particular sources of Ca2+, and the characteristics of Ca2+ signals impacted on autophagy.
The fundamental need for Ca2+ in the activation of autophagy was demonstrated by loading cells with an exogenous Ca2+ buffer, which prevented various stimuli from triggering autophagy.
Autophagy could be activated by inhibiting the transfer of Ca2+ from the endoplasmic reticulum to the mitochondrial matrix. This was achieved by expressing an enzyme that prevented Ca2+ release from inositol 1,4,5-trisphosphate receptors, inhibition of mitochondrial respiration, and knockdown of the mitochondrial Ca2+ uniporter. The triggering of autophagy under these conditions was due to reduced cellular ATP levels. These data suggest that Ca2+ signals arising from InsP3Rs suppress autophagy.
Additional studies used a well-characterised Ca2+ transport pathway to generate cellular Ca2+ signals, and examined their ability to trigger autophagy. This pathway, known as ‘store-operated Ca2+ entry’ (SOCE), was activated by depleting endoplasmic reticulum Ca2+ stores using inhibitors of sarco/endoplasmic reticulum ATPases (SERCA). It was found that sustained cellular Ca2+ signals arising via chronic inhibition of SERCA were pro-autophagic. The activation of autophagy absolutely required the presence of extracellular Ca2+, and was not due to cellular stress. Using pharmacological inhibition of various Ca2+-sensitive kinases, it was found that at least part of the autophagy that occurred during SOCE was due to activation of Ca2+/calmodulin-dependent kinase kinase-β (CaMKK-β, also known as CaMKK-2)."],"dc:format":["application/pdf","application/msword"],"dc:identifier.uri":["https://oro.open.ac.uk/55091/1/__userdata_documents4_tc5664_Desktop_Tala%20Chehab-Thesis.pdf","https://oro.open.ac.uk/55091/8/Thesis%20Deposition%20Form.pdf","https://oro.open.ac.uk/55091/9/GRADPROG%20Memo.doc","https://oro.open.ac.uk/55091/16/Chehab%20-%20Library%20deposition%20memo.doc"],"dc:language":["en"],"dc:publisher.department":["ARRAY(0x7ffb9a484548)"],"dc:publisher.institution":["The Open University"],"dc:relation.isreferencedby":["https://oro.open.ac.uk/55091/"],"dc:title":["The Role of Calcium Signalling in Autophagy"],"dc:type":["Thesis"],"dc:type.qualificationlevel":["doctoral"],"dc:type.qualificationname":["phd"]},"updated_at":"2026-07-24T05:02:52Z"}