Stepana Boukalova

Abstract Why some tumors respond to immunotherapy (“hot” tumors) while others remain resistant (“cold” tumors) is a central challenge in oncology. Elevated RAB5A-dependent endocytosis drives tissue fluidization during the transition to invasive breast carcinoma, but its immunological consequences are unclear. Here we show that RAB5A-driven fluidization induces a mechano-metabolic stress response that disrupts the AMPK–AKAP1–DRP1 mitochondrial fission pathway, causing mitochondrial elongation.

Get full text access Log in, subscribe or purchase for full access. References 1. Tan, A.S. ∙ Baty, J.W. ∙ Dong, L.-F. ... Mitochondrial genome acquisition restores respiratory function and tumorigenic potential of cancer cells without mitochondrial DNA Cell Metab. 2015; 21:81-94 2. Dong, L.-F. ∙ Kovarova, J. ∙ Bajzikova, M. ... Horizontal transfer of whole mitochondria restores tumorigenic potential in mitochondrial DNA-deficient cancer cells eLife. 2017; 6, e22187 3. Dong, L.-F. ∙ Rohlena, J. ∙ Zobalova, R.

Abstract Complex II (CII) activity controls phenomena that require crosstalk between metabolism and signaling, including neurodegeneration, cancer metabolism, immune activation, and ischemia-reperfusion injury. CII activity can be regulated at the level of assembly, a process that leverages metastable assembly intermediates. The nature of these intermediates and how CII subunits transfer between metastable complexes remains unclear.