Mitofusin-2 maintains mitochondrial structure and contributes to stress-induced permeability transition in cardiac myocytes

Kyriakos Papanicolaou, Ramzi J. Khairallah, Gladys A. Ngoh, Aristide Chikando, Ivan Luptak, Karen M. O'Shea, Dushon D. Riley, Jesse J. Lugus, Wilson S. Colucci, W. Jonathan Lederer, William C. Stanley, Kenneth Walsh

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1309-1328
Number of pages20
JournalMolecular and cellular biology
Volume31
Issue number6
DOIs
StatePublished - Mar 1 2011
Externally publishedYes

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Cardiac Myocytes
Permeability
Cell Death
Mitochondrial Dynamics
Dynamins
Cardiomegaly
Mitochondrial Membranes
Reperfusion Injury
Morphogenesis
Reactive Oxygen Species
Mitochondria
Homeostasis
Research
Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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Mitofusin-2 maintains mitochondrial structure and contributes to stress-induced permeability transition in cardiac myocytes. / Papanicolaou, Kyriakos; Khairallah, Ramzi J.; Ngoh, Gladys A.; Chikando, Aristide; Luptak, Ivan; O'Shea, Karen M.; Riley, Dushon D.; Lugus, Jesse J.; Colucci, Wilson S.; Lederer, W. Jonathan; Stanley, William C.; Walsh, Kenneth.

In: Molecular and cellular biology, Vol. 31, No. 6, 01.03.2011, p. 1309-1328.

Research output: Contribution to journalArticle

Papanicolaou, K, Khairallah, RJ, Ngoh, GA, Chikando, A, Luptak, I, O'Shea, KM, Riley, DD, Lugus, JJ, Colucci, WS, Lederer, WJ, Stanley, WC & Walsh, K 2011, 'Mitofusin-2 maintains mitochondrial structure and contributes to stress-induced permeability transition in cardiac myocytes', Molecular and cellular biology, vol. 31, no. 6, pp. 1309-1328. https://doi.org/10.1128/MCB.00911-10
Papanicolaou, Kyriakos ; Khairallah, Ramzi J. ; Ngoh, Gladys A. ; Chikando, Aristide ; Luptak, Ivan ; O'Shea, Karen M. ; Riley, Dushon D. ; Lugus, Jesse J. ; Colucci, Wilson S. ; Lederer, W. Jonathan ; Stanley, William C. ; Walsh, Kenneth. / Mitofusin-2 maintains mitochondrial structure and contributes to stress-induced permeability transition in cardiac myocytes. In: Molecular and cellular biology. 2011 ; Vol. 31, No. 6. pp. 1309-1328.
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