Journal Article

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

Abu Shelbayeh, Othman, Morris, Silke, Busch, Karin B., Arroum, Tasnim

2023

Overview

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,MDPI
• Subject: antioxidants / biogenesis / Biosynthesis / Body fat / Cyclin-dependent kinases / Energy metabolism / Gene expression / Genes / Glucagon / Homeostasis / Immune response / Inflammation / Kinases / Life cycles / Metabolism / Mitochondria / mitochondrial life cycle / mitonuclear communication / Musculoskeletal system / NF-κB protein / Oxidative stress / PGC-1α / Phosphorylation / Physiological aspects / Proteins / Review / RNA polymerase / ROS defense / SIRT1 protein / stress response / transactivators / Transcription factors