title: BCL2-CISD2: An ER complex at the nexus of autophagy and calcium homeostasis?
abstract: CISD2, an ER BCL2-associated autophagy regulator also known as NAF-1, is responsible for the human degenerative disorder Wolfram Syndrome 2. In order to interrogate the physiological role of CISD2 we generated and characterized the Cisd2 gene deletion in mice. Cisd2 null mice manifest significant degeneration in skeletal muscle tissues, which is accompanied with augmented autophagy, dysregulated Ca ( 2+)  homeostasis and elongated mitochondria. Our findings describe a novel role for BCL2-CISD2 in the homeostatic maintenance of skeletal muscle. It remains to be elucidated how and if the antagonism of the BECN1 autophagy-initiating complex and modulation of ER Ca ( 2+)  homeostasis by BCL2-CISD2 are interconnected.
authors.affiliation: Department of Biochemistry and Goodman Cancer Research Center, McGill University, Montréal, Québec, Canada.
authors.forename: Natasha C
authors.initials: NC
authors.lastname: Chang
authors.forename: Mai
authors.initials: M
authors.lastname: Nguyen
authors.forename: Gordon C
authors.initials: GC
authors.lastname: Shore
mesh_terms: D000818:Animals; D001343:Autophagy; D000071183:Autophagy-Related Proteins; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*
chemical_list: D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins; D053496:Inositol 1,4,5-Trisphosphate Receptors; D009419:Nerve Tissue Proteins; C515811:Noxp70 protein, mouse; D019253:Proto-Oncogene Proteins c-bcl-2; D002118:Calcium