How does hypoxia induce autophagy?

Hypoxia (approximately 3-0.1% oxygen) is capable of rapidly inducing, via the hypoxia-inducible factor (HIF-1), a cell survival response engaging autophagy. This process is mediated by the atypical BH3-only proteins the Bcl-2/E1B 19kDa-interacting protein 3 (BNIP3/BNIP3L (NIX)) that are induced by HIF-1.

What does Beclin 1 do in autophagy?

Beclin 1, the mammalian orthologue of yeast Atg6, has a central role in autophagy, a process of programmed cell survival, which is increased during periods of cell stress and extinguished during the cell cycle.

What is BNIP3 gene?

BNIP3 is a member of the apoptotic Bcl-2 protein family. It can induce cell death while also assisting with cell survival. Like many of the Bcl-2 family proteins, BNIP3 modulates the permeability state of the outer mitochondrial membrane by forming homo- and hetero-oligomers inside the membrane.

Can autophagy trigger cell death?

In the germline, autophagy can contribute to cell death in response to genotoxic stress or when apoptotic activity is reduced but does not appear to be essential under normal physiological conditions [54].

Is BNIP3 upregulated under hypoxia?

Although BNIP3 is known to be highly upregulated under hypoxia through the hypoxia-inducible factor (HIF-1), the HIF-1-independent mechanisms and posttranscriptional mechanisms are also crucial for BNIP3 expression in different cells and tissues 14, 15, 16, 17.

Does BNIP3 promote autophagy in hypoxic keratinocytes?

Loss of BNIP3 significantly abrogated the formation of autophagosomes and the overlapping of LC3 and BNIP3 under hypoxia, thereby indicating the induction of autophagy by BNIP3 in hypoxic keratinocytes. Fig. 3: BNIP3 promotes keratinocyte migration through regulation of autophagy.

What is the role of autophagy in the pathogenesis of hypoxia?

Fig. 2: Autophagy is activated in hypoxic keratinocytes and is required for cell migration. Fig. 3: BNIP3 promotes keratinocyte migration through regulation of autophagy. Fig. 4: Increased ROS production induced by hypoxia drives epidermal BNIP3 expression in vivo.

Which autophagy inhibitors are used in the treatment of hypoxia?

Autophagy inhibitors, namely, chloroquine (CQ, 10 μM) and Bafilomycin A1 (BafA1, 10 nM), were added 1 h prior to hypoxia exposure. The extracted proteins were immunoblotted with the indicated antibodies ( d ). e Fluorescence staining of LC3 expression (green) in the indicated HaCaT cells.