Mitochondrial function and actin regulate dynamin-related protein 1-dependent mitochondrial fission

Kurt J. De Vos, Victoria J. Allan, Andrew J. Grierson, Michael Sheetz

Research output: Contribution to journalArticle

222 Citations (Scopus)

Abstract

Mitochondria display a variety of shapes, ranging from small and spherical or the classical tubular shape to extended networks [1, 2]. Shape transitions occur frequently and include fusion, fission, and branching [3]. It was reported that some mitochondrial shape transitions are developmentally regulated [4, 5], whereas others were linked to disease [6-9] or apoptosis [10, 11]. However, if and how mitochondrial function controls mitochondrial shape through regulation of mitochondrial fission and fusion is unclear. Here, we show that inhibitors of electron transport, ATP synthase, or the permeability transition pore (mtPTP) induced reversible mitochondrial fission. Mitochondrial fission depended on dynamin-related protein 1 (DRP1) and F-actin: Disruption of F-actin attenuated fission and recruitment of DRP1 to mitochondria. In contrast, uncoupling of electron transport and oxidative phosphorylation caused mitochondria to adopt a distinct disk shape. This shape change was independent of the cytoskeleton and DRP1 and was most likely caused by swelling. Thus, disruption of mitochondrial function rapidly and reversibly altered mitochondrial shape either by activation of DRP1-dependent fission or by swelling, indicating a close relationship between mitochondrial fission, shape, and function. Furthermore, our results suggest that the actin cytoskeleton is involved in mitochondrial fission by facilitating mitochondrial recruitment of DRP1.

Original languageEnglish (US)
Pages (from-to)678-683
Number of pages6
JournalCurrent Biology
Volume15
Issue number7
DOIs
StatePublished - Apr 12 2005
Externally publishedYes

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Mitochondrial Dynamics
Dynamins
actin
Actins
Mitochondria
Electron Transport
Proteins
proteins
Swelling
Fusion reactions
mitochondria
Oxidative Phosphorylation
electron transfer
Cytoskeleton
Actin Cytoskeleton
Permeability
Adenosine Triphosphate
Chemical activation
dynamins
Apoptosis

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Mitochondrial function and actin regulate dynamin-related protein 1-dependent mitochondrial fission. / De Vos, Kurt J.; Allan, Victoria J.; Grierson, Andrew J.; Sheetz, Michael.

In: Current Biology, Vol. 15, No. 7, 12.04.2005, p. 678-683.

Research output: Contribution to journalArticle

De Vos, Kurt J. ; Allan, Victoria J. ; Grierson, Andrew J. ; Sheetz, Michael. / Mitochondrial function and actin regulate dynamin-related protein 1-dependent mitochondrial fission. In: Current Biology. 2005 ; Vol. 15, No. 7. pp. 678-683.
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