Regulation of sodium-calcium exchange and mitochondrial energetics by Bcl-2 in the heart of transgenic mice.

Abstract:

:Our previous work in cultured cells has shown that the maintenance of mitochondrial Ca(2+) homeostasis is essential for cell survival, and that the anti-apoptotic protein Bcl-2 is able to maintain a threshold level of mitochondrial Ca(2+) by the inhibition of permeability transition. To test whether Bcl-2 also affects the mitochondrial Na(+)-Ca(2+) exchange (NCE), a major efflux pathway for mitochondrial Ca(2+), studies using transgenic mice that overexpress Bcl-2 in the heart have been performed. NCE activity was determined as the Na(+)-dependent Ca(2+) efflux in the isolated mitochondria. Overexpression of Bcl-2 led to a significant reduction of NCE activity as well as increased resistance to permeability transition in the mitochondria of transgenic heart. This was accompanied by increased matrix Ca(2+) level, enhanced formation of NADH and enhanced oxidation of pyruvate, an NAD(+)-linked substrate. Furthermore, there was induction of cellular Ca(2+) transport proteins including the Na(+)-Ca(2+) exchanger of the sarcolemma (NCX). Bcl-2 not only stimulates NCX expression in the sarcolemma but also attenuates the Na(+)-Ca(2+) exchange in the mitochondria. These results are consistent with the protection by Bcl-2 against apoptosis in heart following ischemia/reperfusion.

journal_name

J Mol Cell Cardiol

authors

Zhu L,Yu Y,Chua BH,Ho YS,Kuo TH

doi

10.1006/jmcc.2001.1476

keywords:

subject

Has Abstract

pub_date

2001-12-01 00:00:00

pages

2135-44

issue

12

eissn

0022-2828

issn

1095-8584

pii

S0022-2828(01)91476-2

journal_volume

33

pub_type

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