Figure 3.

HMGB1 and BCL-2 are involved in autophagy and apoptosis. a. In the nucleus, HMGB1 transcriptionally activates HSP27 and results in autophagy by the Pink/Parkin pathway. In the cytoplasm, HMGB1 leads to the dissociation of Beclin-1-BCL-2 complex. Beclin-1/PI3K-III is formed, which then contributes to the initiation of autophagy. Extracellularly, HMGB1 binds to RAGE and activates downstream ERK and AMPK/mTOR pathway, which induces autophagy. b. HMGB1 exert anti-apoptosis role via the intrinsic and extrinsic pathways. HMGB1 can directly targets BCL-2, BAX–BAK channels, caspase-9, and caspase-3. Besides, HMGB1 indirectly targets cytochrome and pro-apoptotic proteins via BCL-2. Red arrows represent activation of the downstream targets, while blue arrows represent suppression of the downstream targets.

HMGB, high mobility group box.