AT-101/gossypol as a trigger of lethal mitophagy. AT-101 causes mitochondrial damage including mitochondrial permeability transition pore (mPTP) opening, loss of membrane potentials, and decreased oxygen consumption. Damaged mitochondria are selectively degraded via mitophagy. In parallel, AT-101 induces the mitophagy receptors BNIP3 and BNIP3L/NIX, as well as the mitophagy-inducer HMOX1, which will further facilitate the extent of mitophagy. This excessive mitophagy finally leads to the demise of the cancer cell(s). This figure was created using Servier Medical Art templates, which are licensed under a Creative Commons Attribution 3.0 Unported License; https://smart.servier.com. From Linder and Kögel, 2019.