Fig. 5: Mitochondrial quality control.
a Healthy mitochondria. The damaged parts of mitochondria split from the healthy parts by split proteins and are encapsulated by autophagosomes for mitochondrial autophagy. While the healthy part of the mitochondria fuses with other mitochondria to achieve its anti-aging function. b Damaged mitochondria. Protein misfolding, mtROS and mtDNA leakage, and oxidative phosphorylation damage can all activate URPmt. URPmt initiation induces ATF4 to bind to CHOP, while ATF5 directly acts on the mitochondrial chaperone promoter, upregulating the expression of HSPA9 and LONP1 to rebuild homeostasis in mitochondria. In addition, PERK further activates the expression of ATF4 by phosphorylating eIF2α, thereby repairing oxidative phosphorylation damage. c Mitochondrial dysfunction. Aging causes decreased expression of PGC-1α and AMPK and impaired ETC, which in turn affects the normal transcription of autophagy genes, upregulates mTOR expression, and leaks ROS and mtDNA, ultimately exacerbating mitochondrial dysfunction.
