Open AccessMitofusin-2 Maintains Mitochondrial Structure and Contributes to Stress-Induced Permeability Transition in Cardiac Myocytes
Author(s) -
Kyriakos N. Papanicolaou,
Ramzi J. Khairallah,
Gladys A. Ngoh,
Aristide C. Chikando,
Ivan Luptak,
Karen M. O’Shea,
Dushon DeVere Riley,
Jesse J. Lugus,
W. Jonathan Lederer,
William C. Stanley,
Kenneth Walsh
Publication year - 2011
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.00911-10
Subject(s) - mitochondrial permeability transition pore , biology , myocyte , microbiology and biotechnology , mitochondrion , mitochondrial fusion , inner mitochondrial membrane , mitochondrial apoptosis induced channel , mitochondrial membrane transport protein , programmed cell death , mitochondrial dna , apoptosis , biochemistry , gene
Mitofusin-2 (Mfn-2) is a dynamin-like protein that is involved in the rearrangement of the outer mitochondrial membrane. Research using various experimental systems has shown that Mfn-2 is a mediator of mitochondrial fusion, an evolutionarily conserved process responsible for the surveillance of mitochondrial homeostasis. Here, we find that cardiac myocyte mitochondria lacking Mfn-2 are pleiomorphic and have the propensity to become enlarged. Consistent with an underlying mild mitochondrial dysfunction, Mfn-2-deficient mice display modest cardiac hypertrophy accompanied by slight functional deterioration. The absence of Mfn-2 is associated with a marked delay in mitochondrial permeability transition downstream of Ca2+ stimulation or due to local generation of reactive oxygen species (ROS). Consequently, Mfn-2-deficient adult cardiomyocytes are protected from a number of cell death-inducing stimuli and Mfn-2 knockout hearts display better recovery following reperfusion injury. We conclude that in cardiac myocytes, Mfn-2 controls mitochondrial morphogenesis and serves to predispose cells to mitochondrial permeability transition and to trigger cell death.