Center for Cell Death, Injury and Regeneration
Autophagy/Mitophagy: Autophagy is the process by which organelles and bits of cytoplasm are sequestered and subsequently delivered to lysosomes for hydrolytic digestion. Autophagy is ongoing in nucleated cells and is typically activated by fasting and nutrient deprivation. In the liver particularly, glucagon promotes autophagy, whereas insulin negatively regulates it. Autophagy is important for generating amino acids, fueling the tricarboxylic cycle, and maintaining ATP energy production. Autophagy also removes unneeded organelles like mitochondria. Timely elimination of aged and dysfunctional mitochondria is essential to protect cells from the harm of disordered mitochondrial metabolism and release of proapoptotic proteins. The mechanism of mitochondrial turnover is predominantly autophagic sequestration and delivery to lysosomes for hydrolytic degradation, a process also called mitophagy. Figure 1 shows that autophagic sequestration of mitochondria in mouse hepatocyte.
Figure 1. Autophagic sequestration of mitochondria and acidification of autophagosomes. GFP-LC3 (green) hepatocytes were loaded with TMRM (red) for 30 min and incubated in KRH/G. Confocal image were taken every minute for 120 min. Arrow and double arrow illustrate the progression of formation of mitophagosomes (mitochondria-containing autophagosomes). In favorable sections along the axis of phagophores, note progression of mitophagy of TMRM-labeled polarized mitochondria from GFP-LC3 PAS patch to cup-shaped phagophore to fully sequestered autophagosomes (mitophagosomes).