Figure 3.

Modulation of autophagy signaling in relation to Sirt3 and autophagy in ovarian cancer. Metformin-mediated Sirt3 overexpression triggers AMPK, which increases activation of LC3. Sirt3 is also involved in autophagy regulation through MAPK/JNK/mTOR autophagy pathway. Several autophagy-related genes, such as beclin-1, p62, LKB1, and VPS34 complex, stimulate autophagy initiation. Sirt3 also activates FOXO3a, which subsequently activates p62 and autophagy. Transcription factor p53 activates and promotes synthesis of autophagy proteins, and high cytoplasmic levels of p53 may result in inhibition of autophagosome formation.