Abstract
Peroxisome proliferator-activated receptor γ (PPARγ) coactivator 1α (PGC-1α) is a master regulator of mitochondrial biogenesis in response to changes in the cellular environment, physiological or pathological status of mammals. PGC-1α is known to be modified by SUMO (Small Ubiquitin-like Modifier). However, it is not known whether SUMOylation could affect the function of PGC-1α in mitochondrial biogenesis and that how PGC-1α SUMOylation is regulated. In this study, we have identified the role of Sentrin/SUMO-specific protease 1 (SENP1) as a specific SUMO protease to regulate SUMOylation status of PGC-1α. More importantly, we have also found that SENP1 promotes PGC-1α transcription activity, which is essential for the expression of mitochondrial genes and subsequently mitochondrial biogenesis. Thus, we reveal that the SUMOylation of PGC-1α controlled by SENP1 plays an important role in mitochondrial biogenesis and function.
Highlights
It is unknown whether SUMOylation could affect the function of PGC-1␣ in mitochondrial biogenesis
It is not known whether SUMOylation could affect the function of PGC-1␣ in mitochondrial biogenesis and that how PGC-1␣ SUMOylation is regulated
We have identified the role of Sentrin/SUMO-specific protease 1 (SENP1) as a specific SUMO protease to regulate SUMOylation status of PGC-1␣
Summary
It is unknown whether SUMOylation could affect the function of PGC-1␣ in mitochondrial biogenesis. We reveal that the SUMOylation of PGC-1␣ controlled by SENP1 plays an important role in mitochondrial biogenesis and function. By analyzing Senp1Ϫ/Ϫ cells, we found that SUMOylation greatly reduced the activation of PGC-1␣ in mitochondrial biogenesis and function.
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