FIGURE 2.

A balanced act of mitophagy and mitochondrial biogenesis. Coordination between mitochondrial (mt) biogenesis and mitophagy results in generation of new synthesized mitochondria, and elimination of detrimental and/or superfluous mitochondria, which is controlled by several signaling pathways, including cyclic-AMP (cAMP)/protein kinase A (PKA), AMP-activated protein kinase (AMPK), mitogen-activated protein kinase (MAPK), and mammalian target of rapamycin (mTOR) signaling, in response to physiological adaptations and stress conditions. Relative to normal condition, increased mitophagy or impaired mt biogenesis will lead to reduced mitochondria mass, contributing to cell death that be dependent on mitochondrial function. Reversely, impaired mitophagy or increased mt biogenesis will lead to imbalanced responses, resulting in increased mitochondria mass, increased reactive oxygen species (ROS) production, and cellular degeneration. However, restoration of mitochondrial homeostasis with increased mitochondrial damage will require simultaneous upregulation of mitophagy and mitochondrial biogenesis.