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Biology, Volume 8, Issue 4 (December 2019)
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Cover Story (view full-size image) The role of autophagy in cell survival and cell death decisions is highly dependent on its extent [...] Read more. The role of autophagy in cell survival and cell death decisions is highly dependent on its extent and on the respective cellular context. A pro-death function of autophagy may be exerted either via nonselective bulk autophagy or excessive (lethal) removal of mitochondria via selective mitophagy, opening new avenues for the therapeutic exploitation of autophagy in apopotisis-resistant cancers such as glioblastoma (GBM). The natural anticancer agent (-)-gossypol (AT-101) causes mitochondrial damage, including mitochondrial permeability transition pore (mPTP) opening, thereby inducing selective degradation of damaged mitochondria via mitophagy. In parallel, AT-101 induces the mitophagy receptors BNIP3 and BNIP3L/NIX, as well as the mitophagy-inducer HMOX1, further enhancing the extent of mitochondrial degradation and culminating in the demise of GBM cells via cell-lethal mitophagy. View this paper