Mitochondrial motility and vascular smooth muscle proliferation

Susan Chalmers, Chris Saunter, Calum Wilson, Paul Coats, John Girkin, John McCarron

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Mitochondria are widely described as being highly dynamic and adaptable organelles and the movement is thought to be vital for cell function. Yet in various native cells, including those of heart and smooth muscle, mitochondria are stationary and rigidly structured. The significance of the differences in mitochondrial behaviour to the physiological function of cells is unclear and was studied in single myocytes and in intact resistance-sized cerebral arteries. We hypothesized that mitochondrial dynamics is controlled by the proliferative status of the cells. High speed fluorescence imaging of mitochondria in live vascular smooth muscle cells shows that the organelle undergoes significant re-organisation as cells become proliferative. In non-proliferative cells mitochondria are individual (~2 um by 0.5 um), stationary, randomly-dispersed, fixed structures. However on entering the proliferative state mitochondria take on a more diverse architecture and become small spheres, short rod shapes, long filamentous entities and networks. When cells are proliferating mitochondria also continuously move and change shape. In the intact pressurized resistance artery mitochondria were largely immobile structures except in a small number of cells in which motility occurred. When proliferation of smooth muscle was encouraged in the intact resistance artery, in organ culture, the majority of mitochondria became motile and the majority of smooth muscle cells contained moving mitochondria. Significantly, restriction of mitochondrial motility using the fission inhibitor Mdivi-1, inhibited vascular smooth muscle proliferation in both single cells and in the intact resistance artery. These results show that mitochondria are adaptable and exist in intact tissue as both stationary and highly dynamic entities. This mitochondrial plasticity is an essential mechanism for the development of smooth muscle proliferation and therefore presents a novel therapeutic target against vascular disease.
LanguageEnglish
Pages3000-3011
Number of pages12
JournalArteriosclerosis Thrombosis, and Vascular Biology
Volume32
Issue number12
Early online date25 Oct 2012
DOIs
Publication statusPublished - Dec 2012

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Vascular Smooth Muscle
Mitochondria
Smooth Muscle
Arteries
Organelles
Smooth Muscle Myocytes
Mitochondrial Dynamics
Muscle Mitochondrion
Cerebral Arteries
Optical Imaging
Organ Culture Techniques
Vascular Diseases
Muscle Cells
Myocardium
Cell Count

Keywords

  • mitochondrial motility
  • vascular smooth muscle
  • arteriosclerosis

Cite this

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Mitochondrial motility and vascular smooth muscle proliferation. / Chalmers, Susan; Saunter, Chris; Wilson, Calum; Coats, Paul; Girkin, John; McCarron, John.

In: Arteriosclerosis Thrombosis, and Vascular Biology, Vol. 32, No. 12, 12.2012, p. 3000-3011.

Research output: Contribution to journalArticle

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AU - Chalmers, Susan

AU - Saunter, Chris

AU - Wilson, Calum

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AU - Girkin, John

AU - McCarron, John

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