STAT3 modulates CD4+ T mitochondrial dynamics and function in aging

Emelia Zukowski, Marco Sannella, Jack Donato Rockhold, Gabriella H. Kalantar, Jingting Yu, Sara SantaCruz-Calvo, Madison K. Kuhn, Nasun Hah, Ling Ouyang, Tzu Wen Wang, Lyanne Murphy, Heather Marszalkowski, Kaleigh Gibney, Micah J. Drummond, Elizabeth A. Proctor, Hatice Hasturk, Barbara S. Nikolajczyk, Leena P. Bharath

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Aging promotes numerous intracellular changes in T cells that impact their effector function. Our data show that aging promotes an increase in the localization of STAT3 to the mitochondria (mitoSTAT3), which promotes changes in mitochondrial dynamics and function and T-cell cytokine production. Mechanistically, mitoSTAT3 increased the activity of aging T-cell mitochondria by increasing complex II. Limiting mitoSTAT3 using a mitochondria-targeted STAT3 inhibitor, Mtcur-1 lowered complex II activity, prevented age-induced changes in mitochondrial dynamics and function, and reduced Th17 inflammation. Exogenous expression of a constitutively phosphorylated form of STAT3 in T cells from young adults mimicked changes in mitochondrial dynamics and function in T cells from older adults and partially recapitulated aging-related cytokine profiles. Our data show the mechanistic link among mitoSTAT3, mitochondrial dynamics, function, and T-cell cytokine production.

Original languageEnglish (US)
Article numbere13996
JournalAging cell
Volume22
Issue number11
DOIs
StatePublished - Nov 2023

All Science Journal Classification (ASJC) codes

  • Aging
  • Cell Biology

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