Traditionally, peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), a 91 kDa transcription factor, regulates lipid metabolism and long-chain fatty acid oxidation by upregulating the expression of several genes of the tricarboxylic acid cycle and the mitochondrial fatty acid oxidation pathway. In addition, PGC-1α regulates the expression of mitochondrial genes to control mitochondria DNA replication and cellular oxidative metabolism. Recently, new insights showed that several myokines such as irisin and myostatin are epigenetically regulated by PGC-1α in skeletal muscles, thereby modulating systemic energy balance, with marked expansion of mitochondrial volume density and oxidative capacity in healthy or diseased myocardia. In addition, in our studies evaluating whether PGC-1α overexpression in epicardial adipose tissue can act as a paracrine organ to improve or repair cardiac function, we found that overexpression of hepatic PGC-1α increased hepatic fatty acid oxidation and decreased triacylglycerol storage and secretion in vivo and in vitro. In this review, we discuss recent studies showing that PGC-1α may regulate mitochondrial fusion–fission homeostasis and affect the renal function in acute or chronic kidney injury. Furthermore, PGC-1α is an emerging protein with a biphasic role in cancer, acting both as a tumor suppressor and a tumor promoter and thus representing a new and unresolved topic for cancer biology studies. In summary, this review paper demonstrates that PGC-1α plays a central role in coordinating the gene expression of key components of mitochondrial biogenesis and as a critical metabolic regulator in many vital organs, including white and brown adipose tissue, skeletal muscle, heart, liver, and kidney.

Activating transcription factor 3 (ATF3) is a stress-induced transcription factor that plays vital roles in modulating metabolism, immunity, and oncogenesis. ATF3 acts as a hub of the cellular adaptive-response network. Multiple extracellular signals, such as endoplasmic reticulum (ER) stress, cytokines, chemokines, and LPS, are connected to ATF3 induction. The function of ATF3 as a regulator of metabolism and immunity has recently sparked intense attention. In this review, we describe how ATF3 can act as both a transcriptional activator and a repressor. We then focus on the role of ATF3 and ATF3-regulated signals in modulating metabolism, immunity, and oncogenesis. The roles of ATF3 in glucose metabolism and adipose tissue regulation are also explored. Next, we summarize how ATF3 regulates immunity and maintains normal host defense. In addition, we elaborate on the roles of ATF3 as a regulator of prostate, breast, colon, lung, and liver cancers. Further understanding of how ATF3 regulates signaling pathways involved in glucose metabolism, adipocyte metabolism, immuno-responsiveness, and oncogenesis in various cancers, including prostate, breast, colon, lung, and liver cancers, is then provided. Finally, we demonstrate that ATF3 acts as a master regulator of metabolic homeostasis and, therefore, may be an appealing target for the treatment of metabolic dyshomeostasis, immune disorders, and various cancers.

Cypher is a member of a recently emerging family of proteins containing a PDZ domain at their NH₂ terminus and one or three LIM domains at their COOH terminus. Cypher knockout mice display a severe form of congenital myopathy and die postnatally from functional failure in multiple striated muscles. Examination of striated muscle from the mutants revealed that Cypher is not required for sarcomerogenesis or Z-line assembly, but rather is required for maintenance of the Z-line during muscle function. In vitro studies demonstrated that individual domains within Cypher localize independently to the Z-line via interactions with α-actinin or other Z-line components. These results suggest that Cypher functions as a linker-strut to maintain cytoskeletal structure during contraction.