MTCH2 promotes BAX and BAK self-assembly and apoptotic pore growth

The uploaded lipidomics dataset contains Liquid Chromatography-Mass Spectrometry (LC-MS) data of cardiolipins and Shotgun Lipidomics data of glycerophospholipids associated to a research project of Hector Flores-Romero et al. from the laboratory of Ana J. Garcia-Saez. The title of the project is: MTCH2 promotes BAX and BAK self-assembly and apoptotic pore growth Project Abstract During apoptosis, the BCL-2 protein family members BAX and BAK oligomerize to mediate the key step of mitochondrial outer membrane permeabilization. However, the contribution of additional cellular components to the apoptotic pore remains poorly understood. Here, we map the protein environment of the apoptotic pore using APEX2-based proximity labelling and identify the mitochondrial carrier homolog protein MTCH2 localizing nearby BAX and BAK assemblies specifically under apoptotic conditions. We show that cells lacking MTCH2 exhibit delayed BAX and BAK oligomerization at the single particle level, which can be rescued by addition of lysophosphatidic acid. Remarkably, MTCH2 depletion decreases mtDNA release into the cytosol and the activation of the cGAS/STING pathway during apoptosis, as well as sublethal mitochondrial permeabilization during bacterial infection. Our findings uncover a new of role of MTCH2 in promoting BAX and BAK assembly with functional consequences for apoptotic pore growth and downstream inflammatory signaling.