Cytoplasmic dynein regulates the subcellular distribution of mitochondria by controlling the recruitment of the fission factor dynamin-related protein-1

Aniko Varadi, Linda I. Johnson-Cadwell, Vincenzo Cirulli, Yisang Yoon, Victoria J. Allan, Guy A. Rutter

Research output: Contribution to journalArticle

176 Citations (Scopus)

Abstract

While the subcellular organisation of mitochondria is likely to influence many aspects of cell physiology, its molecular control is poorly understood. Here, we have investigated the role of the retrograde motor protein complex, dynein-dynactin, in mitochondrial localisation and morphology. Disruption of dynein function, achieved in HeLa cells either by over-expressing the dynactin subunit, dynamitin (p50), or by microinjection of an anti-dynein intermediate chain antibody, resulted in (a) the redistribution of mitochondria to the nuclear periphery, and (b) the formation of long and highly branched mitochondrial structures. Suggesting that an alteration in the balance between mitochondrial fission and fusion may be involved in both of these changes, overexpression of p50 induced the translocation of the fission factor dynamin-related protein (Drp1) from mitochondrial membranes to the cytosol and microsomes. Moreover, a dominant-negative-acting form of Drp1 mimicked the effects of p50 on mitochondrial morphology, while wild-type Drp1 almost completely restored normal mitochondrial distribution in p50 over-expressing cells. Thus, the dynein/dynactin complex plays an unexpected role in the regulation of mitochondrial morphology in living cells, by controlling the recruitment of Drp1 to these organelles.

Original languageEnglish (US)
Pages (from-to)4389-4400
Number of pages12
JournalJournal of Cell Science
Volume117
Issue number19
DOIs
StatePublished - Sep 1 2004

Fingerprint

Cytoplasmic Dyneins
Dynamins
Dyneins
Mitochondria
Proteins
Mitochondrial Dynamics
Cell Physiological Phenomena
Normal Distribution
Microinjections
Mitochondrial Membranes
Microsomes
HeLa Cells
Organelles
Cytosol
Dynactin Complex
Antibodies

Keywords

  • Cytoplasmic dynein
  • Fission
  • Mitochondria
  • Motor proteins

ASJC Scopus subject areas

  • Cell Biology

Cite this

Cytoplasmic dynein regulates the subcellular distribution of mitochondria by controlling the recruitment of the fission factor dynamin-related protein-1. / Varadi, Aniko; Johnson-Cadwell, Linda I.; Cirulli, Vincenzo; Yoon, Yisang; Allan, Victoria J.; Rutter, Guy A.

In: Journal of Cell Science, Vol. 117, No. 19, 01.09.2004, p. 4389-4400.

Research output: Contribution to journalArticle

Varadi, Aniko ; Johnson-Cadwell, Linda I. ; Cirulli, Vincenzo ; Yoon, Yisang ; Allan, Victoria J. ; Rutter, Guy A. / Cytoplasmic dynein regulates the subcellular distribution of mitochondria by controlling the recruitment of the fission factor dynamin-related protein-1. In: Journal of Cell Science. 2004 ; Vol. 117, No. 19. pp. 4389-4400.
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