Regulation of mitochondrial biogenesis

Abstract

Although it is well established that physical activity increases mitochondrial content in muscle, the molecular mechanisms underlying this process have only recently been elucidated. Mitochondrial dysfunction is an important component of different diseases associated with aging, such as Type 2 diabetes and Alzheimer’s disease. PGC-1α (peroxisome-proliferator-activated receptor γ co-activator-1α) is a co-transcriptional regulation factor that induces mitochondrial biogenesis by activating different transcription factors, including nuclear respiratory factor 1 and nuclear respiratory factor 2, which activate mitochondrial transcription factor A. The latter drives transcription and replication of mitochondrial DNA. PGC-1α itself is regulated by several different key factors involved in mitochondrial biogenesis, which will be reviewed in this chapter. Of those, AMPK (AMP-activated protein kinase) is of major importance. AMPK acts as an energy sensor of the cell and works as a key regulator of mitochondrial biogenesis. AMPK activity has been shown to decrease with age, which may contribute to decreased mitochondrial biogenesis and function with aging. Given the potentially important role of mitochondrial dysfunction in the pathogenesis of numerous diseases and in the process of aging, understanding the molecular mechanisms regulating mitochondrial biogenesis and function may provide potentially important novel therapeutic targets.

Human CD8+EMRA T cells display a senescence‐associated secretory phenotype regulated by p38 MAPK

“…2B). Why this should be the case is unclear, but it may be due to the differing roles of CD4 + and CD8 + T cells; furthermore, CD4 + T cells have been shown to have a higher mitochondrial mass than CD8 + T cells (Cao et al ., 2014) regulated by AMPK (Jornayvaz & Shulman, 2010). …”

Targeting Energy Metabolic and Oncogenic Signaling Pathways in Triple-negative Breast Cancer by a Novel Adenosine Monophosphate-activated Protein Kinase (AMPK) Activator

“…3A, OSU-53 treatment led to increased phosphorylation and consequent inactivation of two AMPK downstream targets, ACC and HMGCR, as well as reduced mRNA and protein expression levels of FASN in timeand concentration-dependent manners. Moreover, AMPK has been reported to play a key role in regulating mitochondrial biogenesis in muscle and neuronal cells (31), in part by up-regulating the expression of key regulators of mitochondrial functions, including PCG-1␣, the transcription factor NRF1, and the NRF1 target mtTFA (32). The stimulatory effect of OSU-53 on the PGC-1␣-NRF1 pathway was also noted in treated MDA-MB-231 cells as drug treatment led to concentration-and timedependent increases in the protein and/or mRNA levels of these three key regulators (Fig.…”

Cold tolerance, cold-induced hyperphagia, and nonshivering thermogenesis are normal in α1-AMPK−/−mice

“…Given AMPK's emerging role as a regulator of gene expression and cellular processes such as mitochondrial biogenesis (2, 25), we hypothesized that loss of ␣ 1 -AMPK would prevent or attenuate some of the major physiological changes that occur during chronic cold exposure. We focus on mitochondria, because in skeletal muscle, AMPK has been reported to be a key element in a signaling pathway by which activation of AMPK caused phosphorylation and activation of PPAR-␥ coactivator 1␣, which in turn causes translocation of nuclear regulatory factors and increased synthesis of mitochondrial proteins (18). Instead, wild-type and ␣ 1 -AMPK Ϫ/Ϫ mice were indistinguishable in their response to chronic cold with regard to their body weight, core temperature, and rate of food intake.…”