期刊
BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
卷 1757, 期 5-6, 页码 590-595出版社
ELSEVIER
DOI: 10.1016/j.bbabio.2006.02.007
关键词
mitochondria; permeability transition; VDAC1
资金
- NIGMS NIH HHS [GM69883] Funding Source: Medline
Opening of the permeability transition pore (PTP), a high-conductance mitochondrial channel, causes mitochondrial dysfunction with Ca2+ deregulation, ATP depletion, release of pyridine nucleotides and of mitochondrial apoptogenic proteins. Despite major efforts, the molecular nature of the PTP remains elusive. A compound library screening led to the identification of a novel high affinity PTP inhibitor (Ro 68-3400), which labeled a similar to 32 kDa protein that was identified as isoform I of the voltage-dependent anion channel (VDAC I) [A.M. Cesura, E. Pinard, R. Schubenel, V Goetschy, A. Friedlein, H. Langen, P. Polcic, M.A. Forte, P. Bernardi, J.A. Kemp, The voltage-dependent anion channel is the target for a new class of inhibitors of the mitochondrial permeability transition pore. J. Biol. Chem. 278 (2003) 49812-49818]. In order to assess the role of VDAC I in PTP formation and activity, we have studied the properties of mitochondria from VDACl(-/-) mice. The basic properties of the PTP in VDACI(-/-) mitochondria were indistinguishable from those of strain-matched mitochondria from wild-type CD1 mice, including inhibition by Ro 68-3400, which labeled identical proteins of 32 kDa in both wild-type and VDAC1(-/-) mitochondria. The labeled protein could be separated from all VDAC isoforms. While these results do not allow to exclude that VDAC is part of the PTP, they suggest that VDAC is not the target for PTP inhibition by Ro 68-3400. (c) 2006 Elsevier B.V. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据