Bhavya, B. C. and Deepa, Indira and Mahendra , Seervi and Jeena , Joseph and Praveen, K. Sobhan and Praveen K., Sobhan and Krupa Ann , Mathew and Saneesh , Varghese and T. R. , Santhoshkumar (2012) Endoplasmic Reticulum-Targeted Bcl-2 Inhibitable Mitochondrial Fragmentation Initiates ER Stress-Induced Cell Death. Advances in experimental medicine and biology. pp. 83-95. ISSN 2214-8019

Text Endoplasmic Reticulum-Targeted(Biochemical Roles of Eukaryotic Cell Surface Macromolecules).pdf Restricted to Registered users only Download (455Kb)

Abstract

Endoplasmic reticulum (ER) plays a key role in the maintenance of properly folded proteins, intracellular calcium, modification and trafficking of secretary proteins, etc. Any functional disturbance in ER triggers programmed cell death if reestablishment of homeostasis is failed. Several studies suggest toward a unique ER-centered apoptotic signaling separate from the Bax and Bak-dependent intrinsic apoptosis signaling during ER stress. Here, we show that significant loss of mitochondrial network and fragmentation before cytochrome c release during ER stress initiates the death signaling. The use of Bax-EGFP cells expressing MitoDsRed established that the mitochondrial fragmentation event during ER stress is upstream of Bax activation and its translocation to mitochondria. Caspase inhibitors failed to alter the mitochondrial fragmentation induced by multiple ER stress inducing agents. However, Bcl-2 overexpression specifically at ER significantly prevented early mitochondrial fragmentation and cell death induced by ER stress than the wild type Bcl-2 expressing cells. Our studies suggest that an early caspase-independent mitochondrial fragmentation as an initiating event during ER stress-induced cell death that is under the regulation of Bcl-2 resident at the ER.

Item Type:	Article
Uncontrolled Keywords:	Endoplasmic Reticulum Endoplasmic Reticulum Stress Live Cell Imaging Mitochondrial Fission Mitochondrial Fragmentation
Subjects:	Cancer Research
Depositing User:	Central Library RGCB
Date Deposited:	08 Jul 2019 07:35
Last Modified:	08 Jul 2019 07:35
URI:	http://rgcb.sciencecentral.in/id/eprint/803

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