Promotion of mitochondrial biogenesis by synthetic 1,2‐ or 1,3‐digallates through activation of an energy sensing network

Abstract Based on the observations suggesting that a digallate functionality might serve as a novel scaffold for inducers of mitochondrial biogenesis, we prepared a series of digallates and evaluated their activity in an in vitro model widely used in PD research (SH‐SY5Y cells). Flow cytometry‐based approach revealed stimulation of mitochondrial biogenesis by the gallates, particularly by those with the gallate substituted at the 1,2‐ or 1,3‐ positions. The relative mitochondrial mass calculated after taking cell sizes into account also confirmed the 1,2‐ or 1,3‐digallates as stimulators of mitochondrial biogenesis. Finally, energy sensing network including AMPK, SIRT1, and PGC‐1α was shown to be affected by 1,2‐ or 1,3‐digallates to stimulate mitochondrial biogenesis. Taken together, this study presents a 1,2‐ or 1,3‐ digallate as a novel scaffold for stimulators of mitochondrial biogenesis. As inducers of mitochondrial biogenesis remain scarce, the current findings provide a valuable tool in the battle against neurodegenerative diseases.