title: Mitochondrial motility and vascular smooth muscle proliferation.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom.
authors.forename: Susan
authors.initials: S
authors.lastname: Chalmers
authors.forename: Christopher
authors.initials: C
authors.lastname: Saunter
authors.forename: Calum
authors.initials: C
authors.lastname: Wilson
authors.forename: Paul
authors.initials: P
authors.lastname: Coats
authors.forename: John M
authors.initials: JM
authors.lastname: Girkin
authors.forename: John G
authors.initials: JG
authors.lastname: McCarron
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D002536:Cerebral Arteries / Q000166:cytology / Q000502:physiology; D006168:Guinea Pigs; D007091:Image Processing, Computer-Assisted; D008297:Male; D008856:Microscopy, Fluorescence; D008931:Mitochondria, Muscle / Q000502:physiology*; D063154:Mitochondrial Dynamics / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000502:physiology