Peroxisome proliferator receptor gamma coactivator-lalpha (PGC-lalpha) function in response to low oxygen.

摘要

In order to cope with conditions of low oxygen, the cell can alter its metabolism to survive in the face of reduced capability for oxidative phosphorylation. Peroxisome proliferator receptor gamma coactivator-1alpha (PGC-1alpha), a master regulator of oxidative metabolism, plays a critical role in this response. Under hypoxic conditions, we show that the full-length protein, as well as a truncated form (NT-PGC-1alpha), are upregulated when subjected to a hypoxic event. Under hypoxic conditions, the main function of PGC-1alpha is as a regulator of mitochondrial biogenesis, was inhibited. Both forms of the protein have the ability to be heavily posttranslationally modified. Recent evidence has shown that SUMOylation plays a key role in regulating the proteins activity. The SUMOylation status of both forms of PGC-1alpha under hypoxia were examined. Disruption of the SUMOylation site on PGC-1alpha and NT -PGC-1alpha appeared to play differential roles amongst both forms of the protein, as well as altered the truncated form's ability to undergo further posttranslational modifications.