Anarchy in the UPR: A Ca(2+)-insensitive PKC inhibits SERCA activity to promote ER stress
Nonalcoholic fatty liver disease (NAFLD) is highly prevalent in Western countries, and is linked to the development of liver cancer and Type 2 diabetes (T2D). It is strongly associated with obesity, but the dysregulation of liver lipid storage is not fully understood. Fatty acid oversupply to hepatocytes can establish a vicious cycle involving diminished protein folding, endoplasmic reticulum (ER) stress, insulin resistance and further lipogenesis. This commentary discusses the recent findings of Lai et al. published in Bioscience Reports, that implicate protein kinase C delta (PKCdelta) activation by fatty acids in the inhibition of the SERCA Ca(2+) pump, resulting in reduced ER Ca(2+) loading and protein misfolding. PKCdelta therefore represents a target for the treatment of both steatosis and insulin resistance, key to the prevention of NAFLD and T2D.
|ISBN||1573-4935 (Electronic) 0144-8463 (Linking)|
|Responsible Garvan Author||A/Prof Carsten Schmitz-Peiffer|
|Publisher Name||BIOSCIENCE REPORTS|
|Published Pages||pii: BSR20170966|
|URL link to publisher's version||https://www.ncbi.nlm.nih.gov/pubmed/29439143|
|OpenAccess link to author's accepted manuscript version||https://publications.gimr.garvan.org.au/open-access/14502|