Mild mitochondrial impairment enhances inn3ate immunity and longevity through ATFS-1 and p38 signaling

Author(s)

Campos, Juliane C. ^{[1, 2, 3, 4]} ; Wu, Ziyun ^{[2, 3, 4, 5]} ; Rudich, Paige D. ^{[6, 7, 8]} ; Soo, Sonja K. ^{[6, 7, 8]} ; Mistry, Meeta ^[9] ; Ferreira, Julio C. b ^[1] ; Blackwell, T. Keith ^{[2, 3, 4]} ; Van Raamsdonk, Jeremy M. ^{[2, 6, 7, 8, 10]}

Affiliation

^[1] Univ Sao Paulo, Inst Biomed Sci, Sao Paulo - Brazil

^[2] Harvard Med Sch, Dept Genet, Boston, MA 02115 - USA

^[3] Harvard Med Sch, Harvard Stem Cell Inst, Boston, MA 02115 - USA

^[4] Joslin Diabet Ctr, Res Div, Boston, MA 02215 - USA

^[5] Shanghai Jiao Tong Univ, Sch Agr & Biol, Dept Food Sci & Engn, Shanghai - Peoples R China

^[6] McGill Univ, Dept Neurol & Neurosurg, Montreal, PQ - Canada

^[7] McGill Univ, Res Inst, Hlth Ctr, Metab Disorders & Complicat Program, Montreal, PQ - Canada

^[8] McGill Univ, Res Inst, Hlth Ctr, Brain Repair & Integrat Neurosci Program, Montreal, PQ - Canada

^[9] Harvard Med Sch, Harvard Sch Publ Hlth, Bioinformat Core, Boston, MA 02115 - USA

^[10] McGill Univ, Dept Med, Div Expt Med, Montreal, PQ - Canada

• Document type: Journal article
• Source: EMBO REPORTS; v. 22, n. 12 OCT 2021.
• Web of Science Citations: 0

Abstract

While mitochondrial function is essential for life in all multicellular organisms, a mild impairment of mitochondrial function can extend longevity in model organisms. By understanding the molecular mechanisms involved, these pathways might be targeted to promote healthy aging. In studying two long-lived mitochondrial mutants in C. elegans, we found that disrupting subunits of the mitochondrial electron transport chain results in upregulation of genes involved in innate immunity, which is driven by the mitochondrial unfolded protein response (mitoUPR) but also dependent on the canonical p38-mediated innate immune signaling pathway. Both of these pathways are required for the increased resistance to bacterial pathogens and extended longevity of the long-lived mitochondrial mutants, as is the FOXO transcription factor DAF-16. This work demonstrates that both the p38-mediated innate immune signaling pathway and the mitoUPR act in concert on the same innate immunity genes to promote pathogen resistance and longevity and that input from the mitochondria can extend longevity by signaling through these pathways. This indicates that multiple evolutionarily conserved genetic pathways controlling innate immunity also function to modulate lifespan. (AU)

• FAPESP's process: 19/18444-9 - Mitochondrial dynamics as a limiting factor of exercise-increased healthspan in Caenorhabditis elegans
• Grantee: Juliane Cruz Campos
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor