Lactate and Pyruvate Activate Autophagy and Mitophagy that Protect Cells in Toxic Model of Parkinson's Disease.

Intracellular quality control regulated by autophagy process is important for maintenance of cellular homeostasis. Deregulation of autophagy and more specifically mitophagy leads to accumulation of the misfolded proteins and damaged mitochondria that in turn leads to the cell loss. Alteration of autophagy and mitophagy has shown to be involved in the number of disorders including neurodegenerative diseases. Autophagy and mitophagy could be activated by short-time acidification of the cytosol; however, most of the compounds which can induce it are toxic. Here, we tested several organic compounds which are involved in cellular metabolism on their ability to change intracellular pH and induce mitophagy/autophagy. We have found that lactate and pyruvate are able to reduce intracellular pH in non-toxic concentrations. Short-term (2 h) and long-term (24 h) incubation of the cells with lactate and pyruvateinduced mitophagy and autophagy. Incubation of the SH-SY5Y cells or primary neurons and astrocytes with lactate or pyruvate also activated mitophagy and autophagy after MPP + treatment that led to recovery of mitochondrial function and protection of these cells against apoptotic and necrotic death. Thus, pyruvate- or lactate-induced acidification of cytosol activates cell protective mitophagy and autophagy.