Fabien Franco 800x800

Fabien Franco



15:05 - 15:35

Day 1 – February 1, 2023

Fabien Franco1,2, Ruey-Mei Wu3, Alessio Bevilacqua1,2, Chun-Pu Lin1,2, Lorène Rousseau1,2, Fu-Ti Peng3, Yu-Ming Chuang1,2, Jhan-Jie Peng1,2, Jaeoh Park1,2, Silvia Fuertes Marraco1,Kung-Chi Kao1,2, Antonino Cassotta5, Yi-Ru Yu1,2,Daniel Speiser1, Federica Sallusto4,5 and Ping-Chih Ho1,2

1Department of Fundamental Oncology, University of Lausanne, Epalinges, Switzerland
2Ludwig Institute of Cancer Research Lausanne Branch, Epalinges, Switzerland
3Neurology Department, National Taiwan University Hospital, Taipei, Taiwan
4Institute of Microbiology, ETH Zürich, 8093 Zürich, Switzerland.
5Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland.


Mitophagy, a central guarding process to maintain mitochondrial quality, is commonly impaired in human diseases, such as Parkinson’s disease, but its role in adaptive immunity remains unclear. Notably, differentiation and survival of memory CD8+ T cells rely on oxidative metabolism, a metabolic process that requires a robust mitochondrial quality control. Here, we found that Parkinson’s patients have reduced CD8+ memory T cell abundance and failed to form memory T cells upon COVID-19 vaccination compared to healthy subjects, highlighting the essence of mitochondrial quality control for memory CD8+ T cell formation. We further unveiled that regulators of mitophagy, including Parkin and NIX, were upregulated during memory development in response to IL-15. Deletion of either Parkin or NIX led to severe impairment in memory T cell formation. Mechanistically, Parkin suppressed apoptosis via regulation of VDAC1 in memory T cells; however, NIX expression in T cells prevented ferroptosis by avoiding metabolic dysfunction resulted from impaired mitophagy. Together, our findings indicate that the mitophagy machinery plays a pivotal role during memory T cell formation and highlight the potential approaches to restore T cell-mediated protection for virus infection in Parkinson’s patients.