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Chondrocyte autophagy is stimulated by HIF-1 dependent AMPK activation and mTOR suppression
Pediatric Nephrology, 11/04/09

Bohensky J et al. – The authors inhibited AMPK activity in mTOR silenced cells and showed that while mTOR suppression induced autophagy, AMPK inhibition did not block this activity. Based on these findings, it is concluded that because of the micro–environmental changes experienced by the chondrocyte, autophagy is activated by AMPK in a HIF–1–dependent manner.

Exclusive Author Commentary
Vickram Srinivas, 11/05/09

Bone growth is dependent on the regulated maturation of chondrocytes prior to their deletion from the growth plate; it is this latter step which provides the space for new bone deposition. In the paper, we show that the cells are autophagic, a state which can lead to their continued survival prior to chondrocyte apoptosis. The autophagic state is closely regulated by two environmental factors, the hypoxia inducible factors HIF-1 and-2 and the energetic state of the chondrocyte, mediated by AMP kinase. Disruption of the autophagic flux has been associated with lysosome storage disorders and possibly with skeletal dysplasias.

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