.....We recently reported that GCN5L1, a putative nutrient-sensing regulator, controls mitochondrial removal by autophagy. Here we show that genetic deletion of GCN5L1 has a direct positive effect on the expression and activity of Transcriptional Factor EB (TFEB), which acts as a master regulator of autophagy.
Surprisingly, the induction of TFEB-mediated autophagy pathways does not diminish cellular mitochondrial content, as its activity is countered by induction of the mitochondrial biogenesis transcriptional co-activator PPARγ coactivator 1α (PGC-1α). Concurrent induction of the TFEB and PGC-1α pathways results in an increased mitochondrial turnover rate in GCN5L1(-/-) cells. Finally, we show that genetic knockdown of either TFEB or PGC-1α leads to a corresponding decrease in the expression of the other gene, indicating that these proteins act coordinately, and in opposition, to maintain cellular mitochondrial content in response to the modulation of nutrient-sensing signatures.