Skip to main content

Research Repository

Advanced Search

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.

Authors

Aniko Varadi Aniko.Varadi@uwe.ac.uk
Professor in Biomedical Research

Linda I. Johnson-Cadwell

Vincenzo Cirulli

Yisang Yoon

Victoria J. Allan

Guy A. Rutter



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.

Citation

Varadi, A., Johnson-Cadwell, L. I., Cirulli, V., Yoon, Y., Allan, V. J., & Rutter, G. A. (2004). Cytoplasmic dynein regulates the subcellular distribution of mitochondria by controlling the recruitment of the fission factor dynamin-related protein-1. Journal of Cell Science, 117(19), 4389-4400. https://doi.org/10.1242/jcs.01299

Journal Article Type Article
Publication Date Sep 1, 2004
Journal Journal of Cell Science
Print ISSN 0021-9533
Publisher Company of Biologists
Peer Reviewed Peer Reviewed
Volume 117
Issue 19
Pages 4389-4400
DOI https://doi.org/10.1242/jcs.01299
Keywords cytoplasmic dynein, mitochondria, motor proteins, fission
Public URL https://uwe-repository.worktribe.com/output/1058024
Publisher URL http://dx.doi.org/10.1242/jcs.01299
Additional Information Additional Information : This paper demonstrated a novel concept that cytoplasmic dynein regulates mitochondrial morphology by controlling the recruitment of the dynamin-related protein to these organelles. This work has been extensively reviewed by leading cell biology, genetics and diabetes journals (Nature Reviews in Molecular Cell Biology, Current Biology, Annual Review of Genetics, Diabetes).