AMPK activation of muscle autophagy prevents fasting-induced hypoglycemia and myopathy during aging
Journal article
Bujak, Adam L., Crane, Justin D., Lally, James S., Ford, Rebecca J., Kang, Sally J., Rebalka, Irena A., Green, Alex E., Kemp, Bruce Ernest, Hawke, Thomas J., Schertzer, Jonathan D. and Steinberg, Gregory R.. (2015). AMPK activation of muscle autophagy prevents fasting-induced hypoglycemia and myopathy during aging. Cell Metabolism. 21(6), pp. 883 - 890. https://doi.org/10.1016/j.cmet.2015.05.016
Authors | Bujak, Adam L., Crane, Justin D., Lally, James S., Ford, Rebecca J., Kang, Sally J., Rebalka, Irena A., Green, Alex E., Kemp, Bruce Ernest, Hawke, Thomas J., Schertzer, Jonathan D. and Steinberg, Gregory R. |
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Abstract | The AMP-activated protein kinase ( AMPK ) activates autophagy, but its role in aging and fasting-induced muscle function has not been defined. Here we report that fasting mice lacking skeletal muscle AMPK ( AMPK-MKO ) results in hypoglycemia and hyperketosis. This is not due to defective fatty acid oxidation, but instead is related to a block in muscle proteolysis that leads to reduced circulating levels of alanine, an essential amino acid required for gluconeogenesis. Markers of muscle autophagy including phosphorylation of Ulk1 Ser555 and Ser757 and aggregation of RFP-LC3 puncta are impaired. Consistent with impaired autophagy, aged AMPK-MKO mice possess a significant myopathy characterized by reduced muscle function, mitochondrial disease, and accumulation of the autophagy/mitophagy proteins p62 and Parkin. These findings establish an essential requirement for skeletal muscle AMPK-mediated autophagy in preserving blood glucose levels during prolonged fasting as well as maintaining muscle integrity and mitochondrial function during aging. |
Year | 2015 |
Journal | Cell Metabolism |
Journal citation | 21 (6), pp. 883 - 890 |
Publisher | Cell Press |
ISSN | 1550-4131 |
Digital Object Identifier (DOI) | https://doi.org/10.1016/j.cmet.2015.05.016 |
Scopus EID | 2-s2.0-84930589100 |
Page range | 883 - 890 |
Research Group | Mary MacKillop Institute for Health Research |
Publisher's version | File Access Level Controlled |
Place of publication | United States |
https://acuresearchbank.acu.edu.au/item/8687w/ampk-activation-of-muscle-autophagy-prevents-fasting-induced-hypoglycemia-and-myopathy-during-aging
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