Autophagy Promotes Cell Survival by Maintaining Stable NAD+ Levels: Preclinical Findings

Synopsis

Autophagy is a cellular process that removes damaged parts of the cell and is important for healthy aging. When autophagy is lost, NAD+ levels fall due to increased activity of enzymes that break down NAD+, leading to mitochondrial damage and cell death. This study found that impaired autophagy causes harmful overactivation of NAD-consuming enzymes (PARPs and Sirtuins) in yeast, mouse cells, and human neurons. Blocking this harmful cascade improved survival in all these systems. This work links autophagy to NAD+ metabolism and suggests new targets for diseases involving defective autophagy and mitochondrial dysfunction.

Journal

Developmental Cell