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Review
. 2020 Mar 9:2020:1452696.
doi: 10.1155/2020/1452696. eCollection 2020.

PGC-1 α, Inflammation, and Oxidative Stress: An Integrative View in Metabolism

Sergio Rius-Pérez  1 , Isabel Torres-Cuevas  2 , Iván Millán  2 , Ángel L Ortega  1 , Salvador Pérez  1
Affiliations
Review

PGC-1 α, Inflammation, and Oxidative Stress: An Integrative View in Metabolism

Sergio Rius-Pérez et al. Oxid Med Cell Longev. .

Abstract

Peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α is a transcriptional coactivator described as a master regulator of mitochondrial biogenesis and function, including oxidative phosphorylation and reactive oxygen species detoxification. PGC-1α is highly expressed in tissues with high energy demands, and it is clearly associated with the pathogenesis of metabolic syndrome and its principal complications including obesity, type 2 diabetes mellitus, cardiovascular disease, and hepatic steatosis. We herein review the molecular pathways regulated by PGC-1α, which connect oxidative stress and mitochondrial metabolism with inflammatory response and metabolic syndrome. PGC-1α regulates the expression of mitochondrial antioxidant genes, including manganese superoxide dismutase, catalase, peroxiredoxin 3 and 5, uncoupling protein 2, thioredoxin 2, and thioredoxin reductase and thus prevents oxidative injury and mitochondrial dysfunction. Dysregulation of PGC-1α alters redox homeostasis in cells and exacerbates inflammatory response, which is commonly accompanied by metabolic disturbances. During inflammation, low levels of PGC-1α downregulate mitochondrial antioxidant gene expression, induce oxidative stress, and promote nuclear factor kappa B activation. In metabolic syndrome, which is characterized by a chronic low grade of inflammation, PGC-1α dysregulation modifies the metabolic properties of tissues by altering mitochondrial function and promoting reactive oxygen species accumulation. In conclusion, PGC-1α acts as an essential node connecting metabolic regulation, redox control, and inflammatory pathways, and it is an interesting therapeutic target that may have significant benefits for a number of metabolic diseases.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Structure of PGC-1 family coactivators.
Figure 2
Figure 2
PGC-1α metabolic functions.
Figure 3
Figure 3
PGC-1α signaling pathway in response to ROS/RNS.
Figure 4
Figure 4
Redox regulation of p65 activity by PGC-1α interaction.
Figure 5
Figure 5
PGC-1α downregulation in metabolic syndrome.
See this image and copyright information in PMC

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