FIG. 10.

Regulation of mitochondrial biogenesis machinery by calcium and kinases. Extracellular stimuli increase intracellular calcium levels resulting in kinases activation by transcriptional pathways. Some kinases activate PGC-1α coactivator by transcriptional activation of its gene or by direct phosphorylation, thus resulting in the activation of nuclear respiratory factors NRF-1 and NRF-2 that mediate the transcription of several mitochondrial genes that will promote mitochondrial biogenesis. CaMK, calcium/calmodulin-dependent protein kinase; CREB, cAMP response element-binding protein; ER, endoplasmic reticulum; NRF, nuclear respiratory factor; PGC-1, peroxisome proliferator-activated receptor-γ-coactivator-1; TFAM, mitochondrial transcription factor A.