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202 Mitochondrial Dynamics Regulation of Ros and Apoptosis
  1. Z Al Sulti1,
  2. R McDonald2,
  3. D Kingsmore3,
  4. A Baker2,
  5. P Coats1
  1. 1Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK
  2. 2British Heart Foundation Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow G12 8TA, UK
  3. 3Renal Unit, Western Infirmary, Glasgow, UK

Abstract

Mitochondrial involvement in the control of vascular smooth muscle (VSM) cell proliferation and migration has become more evident than before. Although the mechanisms leading to this control are not fully understood, mitochondrial dynamics and cellular regulation functions can be major players. Studies have revealed that mitochondrial structure and dynamics determines their role played in the cell.1 Mitochondrial proteins were also found to be involved along with mitochondrial miRNAs.2 ATP production to energise cellular functions and ROS resulting from the oxidative phosphorylation are also vital in determining mitochondrial role in VSM cell proliferation and migration3. Mitochondria also regulate the intrinsic apoptotic pathway resulting in reduction in proliferation4. Thus the aim of the current study was to establish a link between mitochondrial dynamics, ROS production and caspase3/7 activation.

Blocking mitochondrial fission using DRP-1 inhibitor resulted in a reduction in VSM cell proliferation in response to PDGF (p < 0.05). The same reduced effect was seen with cell migration following their stimulation with PDGF (p < 0.05). Furthermore, addition of DRP-1 inhibitor resulted in both ROS and ATP (p < 0.05). However, caspase3/7 activity was significantly increased following the inhibition of mitochondrial fission.

These data, along with our previous data showing down-regulation of miR-21 and an up-regulation of miR-145 following treatment with MDivi-1, highlight an important role played by mitochondrial dynamics in the regulation of VSM cell proliferation and migration through the regulation of miRNA expression and their potential target genes that control cell cycle and apoptosis.

References

  1. Chalmers S. et al. Mitochondrial motility and vascular smooth muscle proliferation arterioscler. Thromb Vasc Biol. 2012;32:3000–3011

  2. Barrey E, Saint-Auret G, Bonnamy B, Damas D, Boyer O, Gidrol X. Pre-microRNA and mature microRNA in human mitochondria. PLoS One 2011;6:e20220

  3. Stephen L. Archer, Mardi Gomberg-Maitland. et al. Mitochondrial metabolism, redox signaling, and fusion: a mitochondria-ROS-HIF-1ª¢-Kv1.5 O2-sensing pathway at the intersection of pulmonary hypertension and cancer. Am J Physiol Heart Circ Physiol. 2008;294:H570CH578

  4. Ella Bossy-Wetzel and Green DR. Apoptosis: checkpoint at the mitochondrial frontier. Mutation Research. 1999;434:243C251

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