Mitochondrial motility and vascular smooth muscle proliferation

Susan Chalmers, Christopher Saunter, Calum Wilson, Paul Coats, John M Girkin, John G McCarron

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Mitochondria are widely described as being highly dynamic and adaptable organelles, and their 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 behavior to the physiological function of cells is unclear and was studied in single myocytes and 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 reorganization as cells become proliferative. In nonproliferative cells, mitochondria are individual (≈ 2 μm by 0.5 μm), stationary, randomly dispersed, fixed structures. However, on entering the proliferative state, mitochondria take on a more diverse architecture and become small spheres, short rod-shaped structures, long filamentous entities, and networks. When cells proliferate, mitochondria also continuously move and change shape. In the intact pressurized resistance artery, mitochondria are 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 blocker mitochondrial division inhibitor prevented vascular smooth muscle proliferation in both single cells and 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
DOIs
Publication statusPublished - Dec 2012

Fingerprint

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

Keywords

  • animals
  • cell proliferation
  • cells, cultured
  • cerebral arteries
  • guinea pigs
  • image processing, computer-assisted
  • male
  • microscopy, fluorescence
  • mitochondria, muscle
  • mitochondrial dynamics
  • muscle, smooth, vascular

Cite this

@article{d85a46258869416ab94e70df4098012a,
title = "Mitochondrial motility and vascular smooth muscle proliferation",
abstract = "Mitochondria are widely described as being highly dynamic and adaptable organelles, and their 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 behavior to the physiological function of cells is unclear and was studied in single myocytes and 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 reorganization as cells become proliferative. In nonproliferative cells, mitochondria are individual (≈ 2 μm by 0.5 μm), stationary, randomly dispersed, fixed structures. However, on entering the proliferative state, mitochondria take on a more diverse architecture and become small spheres, short rod-shaped structures, long filamentous entities, and networks. When cells proliferate, mitochondria also continuously move and change shape. In the intact pressurized resistance artery, mitochondria are 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 blocker mitochondrial division inhibitor prevented vascular smooth muscle proliferation in both single cells and 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.",
keywords = "animals, cell proliferation, cells, cultured, cerebral arteries, guinea pigs, image processing, computer-assisted, male, microscopy, fluorescence, mitochondria, muscle, mitochondrial dynamics, muscle, smooth, vascular",
author = "Susan Chalmers and Christopher Saunter and Calum Wilson and Paul Coats and Girkin, {John M} and McCarron, {John G}",
year = "2012",
month = "12",
doi = "10.1161/ATVBAHA.112.255174",
language = "English",
volume = "32",
pages = "3000--3011",
journal = "Arteriosclerosis Thrombosis, and Vascular Biology",
issn = "1079-5642",
number = "12",

}

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

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

Research output: Contribution to journalArticle

TY - JOUR

T1 - Mitochondrial motility and vascular smooth muscle proliferation

AU - Chalmers, Susan

AU - Saunter, Christopher

AU - Wilson, Calum

AU - Coats, Paul

AU - Girkin, John M

AU - McCarron, John G

PY - 2012/12

Y1 - 2012/12

N2 - Mitochondria are widely described as being highly dynamic and adaptable organelles, and their 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 behavior to the physiological function of cells is unclear and was studied in single myocytes and 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 reorganization as cells become proliferative. In nonproliferative cells, mitochondria are individual (≈ 2 μm by 0.5 μm), stationary, randomly dispersed, fixed structures. However, on entering the proliferative state, mitochondria take on a more diverse architecture and become small spheres, short rod-shaped structures, long filamentous entities, and networks. When cells proliferate, mitochondria also continuously move and change shape. In the intact pressurized resistance artery, mitochondria are 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 blocker mitochondrial division inhibitor prevented vascular smooth muscle proliferation in both single cells and 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.

AB - Mitochondria are widely described as being highly dynamic and adaptable organelles, and their 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 behavior to the physiological function of cells is unclear and was studied in single myocytes and 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 reorganization as cells become proliferative. In nonproliferative cells, mitochondria are individual (≈ 2 μm by 0.5 μm), stationary, randomly dispersed, fixed structures. However, on entering the proliferative state, mitochondria take on a more diverse architecture and become small spheres, short rod-shaped structures, long filamentous entities, and networks. When cells proliferate, mitochondria also continuously move and change shape. In the intact pressurized resistance artery, mitochondria are 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 blocker mitochondrial division inhibitor prevented vascular smooth muscle proliferation in both single cells and 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.

KW - animals

KW - cell proliferation

KW - cells, cultured

KW - cerebral arteries

KW - guinea pigs

KW - image processing, computer-assisted

KW - male

KW - microscopy, fluorescence

KW - mitochondria, muscle

KW - mitochondrial dynamics

KW - muscle, smooth, vascular

U2 - 10.1161/ATVBAHA.112.255174

DO - 10.1161/ATVBAHA.112.255174

M3 - Article

VL - 32

SP - 3000

EP - 3011

JO - Arteriosclerosis Thrombosis, and Vascular Biology

T2 - Arteriosclerosis Thrombosis, and Vascular Biology

JF - Arteriosclerosis Thrombosis, and Vascular Biology

SN - 1079-5642

IS - 12

ER -