PGC-1α in Disease: Recent Renal Insights into a Versatile Metabolic Regulator

Abstract

Peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC-1α) is perhaps best known as a master regulator of mitochondrial biogenesis and function. However, by virtue of its interactions as a coactivator for numerous nuclear receptors and transcription factors, PGC-1α also regulates many tissue-specific tasks that include adipogenesis, angiogenesis, gluconeogenesis, heme biosynthesis, thermogenesis, and cellular protection against degeneration. Knowledge about these functions continue to be discovered with ongoing research. Unsurprisingly, alterations in PGC-1α expression lead to a range of deleterious outcomes. In this review, we provide a brief background on the PGC-1 family with an overview of PGC-1α’s roles as an adaptive link to meet cellular needs and its pathological consequences in several organ contexts. Among the latter, kidney health is especially reliant on PGC-1α. Thus, we discuss here at length how changes in PGC-1α function impact the states of renal cancer, acute kidney injury (AKI) and chronic kidney disease (CKD), as well as emerging data that illuminate pivotal roles for PGC-1α during renal development. We survey a new intriguing association of PGC-1α function with ciliogenesis and polycystic kidney disease (PKD), where recent animal studies revealed that embryonic renal cyst formation can occur in the context of PGC-1α deficiency. Finally, we explore future prospects for PGC-1α research and therapeutic implications for this multifaceted coactivator.