OPA1 cleavage depends on decreased mitochondrial ATP level and bivalent metals

被引:88
作者
Baricault, Laurent [1 ]
Segui, Bruno
Guegand, Laurie
Olichon, Aurelien
Valette, Annie
Larminat, Florence
Lenaers, Guy
机构
[1] Univ Toulouse, CNRS, LBCMCP, Toulouse, France
[2] Inst Louis Bugnard, INSERM, U466, Toulouse, France
[3] Univ Montpellier 2, Univ Montpellier 1, Inst Neurosci, INSERM,U583, F-34095 Montpellier 5, France
关键词
mitochondria; OPA1; proteolytic cleavage; membrane dynamic; ATP; bivalent metal cations;
D O I
10.1016/j.yexcr.2007.08.008
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
OPA1, an intra-mitochondrial dynamin GTPase, is a key actor of outer and inner mitochondrial membrane dynamic. OPA1 amino-terminal cleavage by PARL and m-AAA proteases was recently proposed to participate to the mitochondrial network dynamic in a Delta psi(m)-dependent way, and to apoptosis. Here, by an in vitro approach combining the use of purified mitochondrial fractions and mitochondrial targeting drugs, we intended to identify the central stimulus responsible for OPA1 cleavage. We confirm that apoptosis induction and PTPore opening, as well as Delta psi(m), dissipation induce OPA1 cleavage. Nevertheless, our experiments evidenced that decreased mitochondrial ATP levels, either generated by apoptosis induction, Delta psi(m) dissipation or inhibition of ATP synthase, is the common and crucial stimulus that controls OPA1 processing. In addition, we report that ectopic iron addition activates OPA1 cleavage, whereas zinc inhibits this process. These results suggest that the ATP-dependent OPA1 processing plays a central role in correlating the energetic metabolism to mitochondrial dynamic and might be involved in the pathophysiology of diseases associated to excess of iron or depletion of zinc and ATP. (C) 2007 Elsevier Inc. All rights reserved.
引用
收藏
页码:3800 / 3808
页数:9
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