348245.fig.001
Figure 1: A well-controlled regulation of mitochondrial quality via mitochondrial biogenesis and mitophagy. Mitophagy, in conjunction with mitochondrial biogenesis, regulates the changes in mitochondrial number that are required to meet metabolic demand. Activated AMPK acutely triggers ULK1-dependent mitophagy and simultaneously triggers the biogenesis of new mitochondria via effects on PGC-1α-dependent transcription. Conversely, mTOR represses mitochondrial biogenesis and ULK1-dependent mitophagy when nutrients are plentiful. These dual processes controlled by AMPK and mTOR determine the net effect of replacing defective mitochondria with new functional mitochondria. AMPK: AMP-activated protein kinase; mTOR: mammalian target of rapamycin; PGC-1α: PPARgamma coactivator 1-alpha; ULK1: the mammalian Atg1 homologs, uncoordinated family member (unc)-51: like kinase 1; ERK2: the extracellular signal-regulated protein kinase 2; U0126: ERK inhibitor.