PGC-1α Is a Master Regulator of Mitochondrial Lifecycle and ROS Stress Response

Author:

Abu Shelbayeh Othman1,Arroum Tasnim12ORCID,Morris Silke1,Busch Karin B.1

Affiliation:

1. Institute of Integrative Cell Biology and Physiology, University of Münster, Schlossplatz 5, 48149 Münster, Germany

2. Molecular Medicine and Genetics, Wayne State University, Detroit, MI 48202, USA

Abstract

Mitochondria play a major role in ROS production and defense during their life cycle. The transcriptional activator PGC-1α is a key player in the homeostasis of energy metabolism and is therefore closely linked to mitochondrial function. PGC-1α responds to environmental and intracellular conditions and is regulated by SIRT1/3, TFAM, and AMPK, which are also important regulators of mitochondrial biogenesis and function. In this review, we highlight the functions and regulatory mechanisms of PGC-1α within this framework, with a focus on its involvement in the mitochondrial lifecycle and ROS metabolism. As an example, we show the role of PGC-1α in ROS scavenging under inflammatory conditions. Interestingly, PGC-1α and the stress response factor NF-κB, which regulates the immune response, are reciprocally regulated. During inflammation, NF-κB reduces PGC-1α expression and activity. Low PGC-1α activity leads to the downregulation of antioxidant target genes resulting in oxidative stress. Additionally, low PGC-1α levels and concomitant oxidative stress promote NF-κB activity, which exacerbates the inflammatory response.

Publisher

MDPI AG

Subject

Cell Biology,Clinical Biochemistry,Molecular Biology,Biochemistry,Physiology

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