Mitofusins Mfn1 and Mfn2 coordinately regulate mitochondrial fusion and are essential for embryonic development

Hsiuchen Chen, Scott A. Detmer, Andrew Ewald, Erik E. Griffin, Scott E. Fraser, David C. Chan

Research output: Contribution to journalArticle

Abstract

Mitochondrial morphology is determined by a dynamic equilibrium between organelle fusion and fission, but the significance of these processes in vertebrates is unknown. The mitofusins, Mfn1 and Mfn2, have been shown to affect mitochondrial morphology when overexpressed. We find that mice deficient in either Mfn1 or Mfn2 die in midgestation. However, whereas Mfn2 mutant embryos have a specific and severe disruption of the placental trophoblast giant cell layer, Mfn1-deficient giant cells are normal. Embryonic fibroblasts lacking Mfn1 or Mfn2 display distinct types of fragmented mitochondria, a phenotype we determine to be due to a severe reduction in mitochondrial fusion. Moreover, we find that Mfn1 and Mfn2 form homotypic and heterotypic complexes and show, by rescue of mutant cells, that the homotypic complexes are functional for fusion. We conclude that Mfn1 and Mfn2 have both redundant and distinct functions and act in three separate molecular complexes to promote mitochondrial fusion. Strikingly, a subset of mitochondria in mutant cells lose membrane potential. Therefore, mitochondrial fusion is essential for embryonic development, and by enabling cooperation between mitochondria, has protective effects on the mitochondrial population.

Original languageEnglish (US)
Pages (from-to)189-200
Number of pages12
JournalJournal of Cell Biology
Volume160
Issue number2
DOIs
StatePublished - Jan 20 2003
Externally publishedYes

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Mitochondrial Dynamics
Embryonic Development
Mitochondria
Giant Cells
Trophoblasts
Organelles
Membrane Potentials
Vertebrates
Embryonic Structures
Fibroblasts
Cell Membrane
Phenotype
Population

Keywords

  • GTPase
  • Knockout
  • Membrane fusion
  • Mice
  • Mitochondria

ASJC Scopus subject areas

  • Cell Biology

Cite this

Mitofusins Mfn1 and Mfn2 coordinately regulate mitochondrial fusion and are essential for embryonic development. / Chen, Hsiuchen; Detmer, Scott A.; Ewald, Andrew; Griffin, Erik E.; Fraser, Scott E.; Chan, David C.

In: Journal of Cell Biology, Vol. 160, No. 2, 20.01.2003, p. 189-200.

Research output: Contribution to journalArticle

Chen, Hsiuchen ; Detmer, Scott A. ; Ewald, Andrew ; Griffin, Erik E. ; Fraser, Scott E. ; Chan, David C. / Mitofusins Mfn1 and Mfn2 coordinately regulate mitochondrial fusion and are essential for embryonic development. In: Journal of Cell Biology. 2003 ; Vol. 160, No. 2. pp. 189-200.
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