Abstract: In kidney, proximal tubules consume a large amount of energy to support electrolyte homeostasis. These tubules contain large quantities of mitochondria, which provide the energy for the electrolyte reabsorption. Proximal tubules are susceptible to many kinds of insults such as ischemia-reperfusion injury and nephrotoxic substrates, but little is known about the factors that counteract the cellular stress signaling pathways in tubular epithelial cells. Autophagy mediates bulk degradation and recycling of cytoplasmic constituents to maintain cellular homeostasis. We demonstrated the critical role of autophagy in normal proximal tubule function and protection against acute tubular injury.