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Vol. 13, Issue 12, 4343-4354, December 2002
Institut National de la Santé et de la Recharche
Médicale U523, Institut de Myologie, Groupe Hospitalier
Pitié-Salpêtrière, 75651 Paris, France
Mitochondrial fusion remains a largely unknown process
despite its observation by live microscopy and the identification of few implicated proteins. Using green and red fluorescent proteins targeted to the mitochondrial matrix, we show that mitochondrial fusion
in human cells is efficient and achieves complete mixing of matrix
contents within 12 h. This process is maintained in the absence of
a functional respiratory chain, despite disruption of microtubules or
after significant reduction of cellular ATP levels. In contrast,
mitochondrial fusion is completely inhibited by protonophores that
dissipate the inner membrane potential. This inhibition, which results
in rapid fragmentation of mitochondrial filaments, is reversible: small
and punctate mitochondria fuse to reform elongated and interconnected
ones upon withdrawal of protonophores. Expression of wild-type or
dominant-negative dynamin-related protein 1 showed that
fragmentation is due to dynamin-related protein 1-mediated
mitochondrial division. On the other hand, expression of mitofusin 1 (Mfn1), one of the human Fzo homologues, increased mitochondrial length
and interconnectivity. This process, but not Mfn1 targeting, was
dependent on the inner membrane potential, indicating that
overexpressed Mfn1 stimulates fusion. These results show that human
mitochondria represent a single cellular compartment whose exchanges
and interconnectivity are dynamically regulated by the balance between
continuous fusion and fission reactions.
Online version of this article contains video material for some
figures. Online version available at www.molbiolcell.org.
*
Corresponding author. E-mail address:
m.rojo{at}myologie.chups.jussieu.fr.
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