Amphiphilic β-sheet cobra cardiotoxin targets mitochondria and disrupts its network

Wang, Chia-Hui; Wu, Wen-guey

doi:10.1016/j.febslet.2005.05.006

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Volume 579, Issue 14 , Pages 3169-3174, 6 June 2005

Amphiphilic β-sheet cobra cardiotoxin targets mitochondria and disrupts its network

Edited by Maurice Montal

Department of Life Sciences, Institute of Bioinformatics and Structural Biology, National Tsinghua University, 101, Section 2, Kuang Fu Road, Hsinchu 30013, Taiwan

Received 29 March 2005; received in revised form 2 May 2005; accepted 2 May 2005. published online 23 May 2005.

Abstract

Recent advance in understanding the role of toxin proteins in controlling cell death has revealed that pro-apoptotic viral proteins targeting mitochondria contain amphiphilic α-helices with pore-forming properties. Herein, we describe that the pore-forming amphiphilic β-sheet cardiotoxins (or cytotoxins, CTXs) from Taiwan cobra (Naja atra) also target mitochondrial membrane after internalization and act synergistically with CTX-induced cytosolic calcium increase to disrupt mitochondria network. It is suggested that CTX-induced fragmentation of mitochondria play a role in controlling CTX-induced necrosis of myocytes and cause severe tissue necrosis in the victims.

Abbreviations: BAPTA-AM, (acetoxymethyl)-1,2-bis(o-aminophenoxy)ethane N,N,N′,N′-tetraacetic acid, CT B, Cholera toxin B, CTX, cytotoxin or cardiotoxin, ER, endoplasmic reticulum, FCCP, carbonyl cyanide p-[trifluoromethoxy]-phenyl-hydrazone, FITC, fluorescein isothiocyanate, HBSS, Hanks’ balanced salt solution, HPLC, high performance liquid chromatography