期刊
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
卷 286, 期 4, 页码 G671-G682出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpgi.00283.2003
关键词
myenteric neuron; axonal transport; intracellular calcium stores; MitoTracker
资金
- NIDDK NIH HHS [P01-DK-41315] Funding Source: Medline
Enteric neurons controlling various gut functions are prone to oxidative insults that might damage mitochondria (e.g., intestinal inflammation). To resume local energy supply, mitochondria need to be transported. We used MitoTracker dyes and confocal microscopy to investigate basic characteristics of mitochondrial transport in guinea pig myenteric neurites. During a 10-s observation of 1 mm nerve fiber, on average, three mitochondria were transported at an average speed of 0.41+/-0.02 mum/s. Movement patterns were clearly erratic, and velocities were independent of mitochondrial size. The velocity oscillated periodically (similar to6 s) but was not consistently affected by structures such as en route boutons, bifurcations, or stationary mitochondria. Also, mitochondria transported in opposite directions did not necessarily affect each others' mobility. Transport was blocked by microtubule disruption (100 muM colchicine), and destabilization (1 muM cytochalasin-D) or stabilization (10 muM phalloidin) of actin filaments, respectively, decreased (0.22+/-0.02 mum/s, P<0.05) or increased (0.53 +/- 0.02 mu m/s, P<0.05) transport speed. Transport was inhibited by TTX (1 muM), and removal of extracellular Ca2+ (plus 2 mM EGTA) had no effect. However, depletion of intracellular stores (thapsigargin) reduced (to 33%) and slowed the transport significantly (0.18+/-0.02 mum/s, P<0.05), suggesting an important role for stored Ca2+ in mitochondrial transport. Transport was also reduced (to 21%) by the mitochondrial uncoupler FCCP (1 mu M) in a time-dependent fashion and slowed by oligomycin (10 mu M). We conclude that mitochondrial transport is remarkably independent of structural nerve fiber properties. We also show that mitochondrial transport is TTX sensitive and speeds up by stabilizing actin and that functional Ca2+ stores are required for efficient transport.
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