Age decreases mitochondrial motility and increases mitochondrial size in vascular smooth muscle

Chalmers, S.; Saunter, C.D.; Girkin, J.M.; McCarron, J.G.

Abstract

Mitochondrial function, motility and architecture are each central to cell function. Age-associated mitochondrial dysfunction may contribute to vascular disease. However, mitochondrial changes in ageing remain ill-defined because of the challenges of imaging in native cells. We determined the structure of mitochondria in live native cells, demarcating boundaries of individual organelles by inducing stochastic ‘flickers’ of membrane potential, recorded as fluctuations in potentiometric fluorophore intensity (flicker-assisted localization microscopy; FaLM). In freshly-isolated myocytes from rat cerebral resistance arteries, FaLM showed a range of mitochondrial X-Y areas in both young adult (3 months; 0.05–6.58 μm2) and aged rats (18 months; 0.05–13.4 μm2). In cells from young animals, most mitochondria were small (mode area 0.051 μm2) compared to aged animals (0.710 μm2). Cells from older animals contained a subpopulation of highly-elongated mitochondria (5.3% were >2 μm long, 4.2% had a length:width ratio >3) that was rare in younger animals (0.15% of mitochondria >2 μm long, 0.4% had length:width ratio >3). The extent of mitochondrial motility also varied. 1/811 mitochondria observed moved slightly (∼0.5 μm) in myocytes from older animals, whereas, in the younger animals, directed and Brownian-like motility occurred regularly (215 of 1135 mitochondria moved within 10 min, up to distance of 12 μm). Mitochondria positioned closer to the cell periphery showed a greater tendency to move. In conclusion, cerebral vascular myocytes from young rats contained small, motile mitochondria. In aged rats, mitochondria were larger, immobile and could be highly-elongated. These age-associated alterations in mitochondrial behaviour may contribute to alterations in cell signalling, energy supply or the onset of proliferation.

Citation

Chalmers, S., Saunter, C., Girkin, J., & McCarron, J. (2016). Age decreases mitochondrial motility and increases mitochondrial size in vascular smooth muscle. The Journal of Physiology, 594(15), 4283-4295. https://doi.org/10.1113/jp271942

• Journal Article Type: Article
• Acceptance Date: Feb 26, 2016
• Online Publication Date: Apr 9, 2016
• Publication Date: Aug 1, 2016
• Deposit Date: Apr 11, 2016
• Publicly Available Date: Apr 11, 2016
• Journal: Journal of Physiology
• Print ISSN: 0022-3751
• Electronic ISSN: 1469-7793
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 594
• Issue: 15
• Pages: 4283-4295
• DOI: https://doi.org/10.1113/jp271942
• Public URL: https://durham-repository.worktribe.com/output/1407120