AMP-activated protein kinase (AMPK) has an important role in regulating cellular energy equilibrium. It acts as a cellular energy sensor and can respond to low levels of ATP in the body (Jornayvaz & Shulman, 2010). AMPK activation can positively regulates signaling pathways that are involved in replenishing cellular ATP supplies, fatty acid oxidation, lipogenesis, and triglyceride synthesis. AMPK is not only involved in mitochondrial biogenesis, but it is also involved in biogenesis of glucose transporter 4 (GLUT 4) (Dominy & Puigserver, 2013). Research shows that AMPK increases mitochondrial biogenesis by inducing peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) transcription (Fernandez-Marcos & Auwerx, 2011). PGC-1α is a protein that is involved in the regulation of genes that are important in energy metabolism. Exercise can activate the protein in human skeletal muscles. This protein starts working actively in the presence of other factors. It binds different factors PPARγ and nuclear respiratory factor (NRF) -1. It also recruits proteins having HAT activity such as CREB binding protein (CBP/p300 ), SRC-1, and other HATs to move out of the quiescent state and start activity. After the activation of PGC-1α, it results in the induction as well as coordination of gene expression, thereby stimulating mitochondrial oxidative metabolism (Puigserver & Spiegelman, 2003).
No known studies have been found regarding the direct recruitment of HAT1 by PGC-1α, which has an important role in AMPK function and control energy homeostasis. However, it can be assumed that AMPK induces PGC-1α that interacts with Hat1, whose catalytic domains are thought to be structurally related to that of other HAT enzymes such as CBP and Gcn5. Moreover, HAT activity of Hat1 is increased in the presence of a partner, Hat2, and both of them joins PGC-1α (Dutnall, Tafrov, Sternglanz, & Ramakrishnan, 1998).
Dominy, J. E., & Puigserver, P. (2013). Mitochondrial biogenesis through activation of nuclear signaling proteins. Cold Spring Harbor perspectives in biology, 5(7), a015008.
Dutnall, R. N., Tafrov, S. T., Sternglanz, R., & Ramakrishnan, V. (1998). Structure of the Histone Acetyltransferase Hat1. Cell, 94(4), 427-438. doi: 10.1016/s0092-8674(00)81584-6
Fernandez-Marcos, P. J., & Auwerx, J. (2011). Regulation of PGC-1alpha, a nodal regulator of mitochondrial biogenesis. Am J Clin Nutr, 93(4), 884S-890. doi: 10.3945/ajcn.110.001917
Jornayvaz, F. R., & Shulman, G. I. (2010). Regulation of mitochondrial biogenesis. Essays Biochem, 47, 69-84. doi: 10.1042/bse0470069
Puigserver, P., & Spiegelman, B. M. (2003). Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha): transcriptional coactivator and metabolic regulator. Endocr Rev, 24(1), 78-90. doi: 10.1210/er.2002-0012