MCL-1 is essential for survival but dispensable for metabolic fitness of FOXP3( )regulatory T cells
Charis E Teh, Alissa K Robbins, Darren C Henstridge, Grant Dewson, Sarah T Diepstraten, Gemma Kelly, Mark A Febbraio, Sarah S Gabriel, Lorraine A O'Reilly, Andreas Strasser, Daniel HD Gray
CELL DEATH AND DIFFERENTIATION | SPRINGERNATURE | Published : 2020
FOXP3+ regulatory T (Treg) cells are essential for maintaining immunological tolerance. Given their importance in immune-related diseases, cancer and obesity, there is increasing interest in targeting the Treg cell compartment therapeutically. New pharmacological inhibitors that specifically target the prosurvival protein MCL-1 may provide this opportunity, as Treg cells are particularly reliant upon this protein. However, there are two distinct isoforms of MCL-1; one located at the outer mitochondrial membrane (OMM) that is required to antagonize apoptosis, and another at the inner mitochondrial membrane (IMM) that is reported to maintain IMM structure and metabolism via ATP production duri..View full abstract
Awarded by National Health and Medical Research Council Australia
Awarded by Leukemia and Lymphoma Society
We thank A. Rudensky, B. Kile, and P. Bouillet for provision of mice and D. Huang, J. Gong, and A. Kallies for reagents. We are grateful to the WEHI Flow Cytometry Laboratory and Bioservices staff for technical support (particularly H. Marks and G. Siciliano for mouse husbandry) and B. Helbert, C Young, and K. Mackwell for genotyping. This work was supported by National Health and Medical Research Council Australia (Grants or Fellowships 1089072 to CET, 1116936 to MAF, and 1078763, 1090236, 1145888, and 1158024 to DHDG), Fellowships by Swiss National Science Foundation and Novartis Foundation for Medical-Biological Research to SSG and Leukemia and Lymphoma Society (Special Centre of Research Grant 7015-18) to GK. This research was made possible by grants from the Victorian State Government Operational Infrastructure Support and the Independent Research Institutes Infrastructure Support Scheme of the Australian Government National Health and Medical Research Council.