TY - JOUR
T1 - Mitofusin-2 maintains mitochondrial structure and contributes to stress-induced permeability transition in cardiac myocytes
AU - Papanicolaou, Kyriakos N.
AU - Khairallah, Ramzi J.
AU - Ngoh, Gladys A.
AU - Chikando, Aristide
AU - Luptak, Ivan
AU - O'Shea, Karen M.
AU - Riley, Dushon D.
AU - Lugus, Jesse J.
AU - Colucci, Wilson S.
AU - Lederer, W. Jonathan
AU - Stanley, William C.
AU - Walsh, Kenneth
PY - 2011/3
Y1 - 2011/3
N2 - 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.
AB - 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.
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U2 - 10.1128/MCB.00911-10
DO - 10.1128/MCB.00911-10
M3 - Article
C2 - 21245373
AN - SCOPUS:79952265711
SN - 0270-7306
VL - 31
SP - 1309
EP - 1328
JO - Molecular and cellular biology
JF - Molecular and cellular biology
IS - 6
ER -