Cross-talk Between Autophagy and Mitophagy Regulates Shear-induced Nitric Oxide Production in Endothelial Cells

Aging is associated with suppressed endothelial cell (EC) autophagy and EC nitric oxide (NO) bioavailability. A link might exist among autophagy, mitophagy, and stimulated NO production in ECs. ECs treated with scrambled siRNA exposed to shear stress (3 h x 20 dyn/cm2) exhibit: ↑LC3-II:LC3-1, ↓p62, ↑LC3-GFP puncta formation (indices of increased autophagy); ↓VDAC, ↓m-aconitase, ↑TOM20:LAMP1 colocalization, ↓ mitochondrial pH indicating lysosomal compartmentalization (indices of increased mitochondrial turnover), ↑ROS generation, ↑endothelial NO synthase (eNOS) phosphorylation, and ↑NO production (p<0.05 for all). ECs transfected with AuTophaGy-related protein 3 (Atg3) siRNA did not exhibit shear-induced autophagy, mitochondrial turnover, eNOS phosphorylation, or NO production, but ROS accumulation and cytokine production (ICAM-1, MCP-1, IL-8, E-selectin) were exaggerated (all p<0.05). Shear-induced increases in oxygen consumption rate, extracellular acidification rate, and ATP production (all p<0.05) in E...