Functional implications of mitofusin 2-mediated mitochondrial-SR tethering

被引：65

作者：

Dorn, Gerald W., II ^{[1
]}

Song, Moshi ^{[1
]}

Walsh, Kenneth ^{[2
]}

机构：

[1] Washington Univ, Sch Med, Ctr Phaimacogen, Dept Internal Med, St Louis, MO 63110 USA

[2] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA

来源：

JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY | 2015年 / 78卷

关键词：

Mitochondria; Sarcoplasmic reticulum; Calcium cross-talk; Organelle tethering; Mitochondrial fusion; Mitochondrial permeability transition pore; ENDOPLASMIC-RETICULUM STRESS; CARDIAC MYOCYTES; CELL-DEATH; PERMEABILITY TRANSITION; CALCIUM UNIPORTER; CA2+; FUSION; MEMBRANE; PROTEIN; CARDIOMYOPATHY;

D O I：

10.1016/j.yjmcc.2014.09.015

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Cardiomyocyte mitochondria have an intimate physical and functional relationship with sarcoplasmic reticulum (SR). Under normal conditions mitochondrial ATP is essential to power SR calcium cycling that drives phasic contraction/relaxation, and changes in SR calcium release are sensed by mitochondria and used to modulate oxidative phosphorylation according to metabolic need. When perturbed, mitochondrial-SR calcium crosstalk can evoke programmed cell death. Physical proximity and functional interplay between mitochondria and SR are maintained in part through tethering of these two organelles by the membrane protein mitofusin 2 (Mfn2). Here we review and discuss findings from our two laboratories that derive from genetic manipulation of Mfn2 and closely related Mfn1 in mouse hearts and other experimental systems. By comparing the findings of our two independent research efforts we arrive at several conclusions that appear to be strongly supported, and describe a few areas of incomplete understanding that will require further study. In so doing we hope to clarify some misconceptions regarding the many varied roles of Mfn2 as both physical trans-organelle tether and mitochondrial fusion protein. This article is part of a Special Issue entitled "Mitochondria: From Basic Mitochondrial Biology to Cardiovascular Disease." (C) 2014 Elsevier Ltd. All rights reserved.

引用

页码：123 / 128

页数：6

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