The effect of HSF‐1 and HSP70 on autophagy regulation

Abstract

Autophagy is an evolutionarily conserved mechanism that plays an important role in maintaining cellular homeostasis by recycling large protein aggregates, damaged proteins, entire organelles, and bulk of cytoplasm within double membrane vacuoles delivered for degradation to lysosomes. Heat stress response renders protection to macromolecules, cells, as well as whole organism by assisting in folding of newly synthesized proteins, in stabilizing of unfolded protein, and in degradation and reactivation of damaged proteins. Previously, we have reported that autophagy is regulated by heat stress response. The purpose of the study was to investigate the role of heat shock factor 1 (HSF‐1), the central regulator of heat shock response and heat shock protein 70 (HSP70), principal effector of heat shock response on starvation‐induced autophagy in A549 cells. We utilized HSF‐1 siRNA to inhibit HSF‐1 protein expression and adenovirus to overexpress inducible form of HSP70. Their effects on starvation‐ induced autophagy were tested. Exposure to HSF‐1 siRNA augmented the starvation‐induced increase in autophagy and HSP70 significantly blocked this increase. We conclude that heat stress response exert a regulatory role on autophagy.