Highlights d Sirt3 SUMOylation suppresses its catalytic activity in mitochondria d Fasting induces SENP1 translocation into mitochondria to de-SUMOylate Sirt3 d The SENP1-Sirt3 axis promotes fatty acid oxidation and energy production d Sirt3 SUMOylation mutation antagonizes HFD-induced obesity via energy expenditure

Metabolic programming and mitochondrial dynamics along with T cell differentiation affect T cell fate and memory development; however, how to control metabolic reprogramming and mitochondrial dynamics in T cell memory development is unclear. Here, we provide evidence that the SUMO protease SENP1 promotes T cell memory development via Sirt3 deSUMOylation. SENP1-Sirt3 signalling augments the deacetylase activity of Sirt3, promoting both OXPHOS and mitochondrial fusion. Mechanistically, SENP1 activates Sirt3 deacetylase activity in T cell mitochondria, leading to reduction of the acetylation of mitochondrial metalloprotease YME1L1. Consequently, deacetylation of YME1L1 suppresses its activity on OPA1 cleavage to facilitate mitochondrial fusion, which results in T cell survival and promotes T cell memory development. We also show that the glycolytic intermediate fructose-1,6-bisphosphate (FBP) as a negative regulator suppresses AMPK-mediated activation of the SENP1-Sirt3 axis and reduces memory development. Moreover, glucose limitation reduces FBP production and activates AMPK during T cell memory development. These data show that glucose limitation activates AMPK and the subsequent SENP1-Sirt3 signalling for T cell memory development.

Introduction: Given the ongoing coronavirus disease 2019 (COVID-19) pandemic and the consequent global healthcare crisis, there is an urgent need to better understand risk factors for symptom deterioration and mortality among patients with COVID-19. This systematic review aimed to meet the need by determining the predictive value of chronic diseases for COVID-19 severity and mortality.Methods: We searched PubMed, Embase, Web of Science, and Cumulative Index to Nursing and Allied Health Complete to identify studies published between December 1, 2019, and December 31, 2020. Two hundred and seventeen observational studies from 26 countries involving 624,986 patients were included. We assessed the risk of bias of the included studies and performed a cumulative meta-analysis.Results: We found that among COVID-19 patients, hypertension was a very common condition and was associated with higher severity, intensive care unit (ICU) admission, acute respiratory distress syndrome, and mortality. Chronic obstructive pulmonary disease was the strongest predictor for COVID-19 severity, admission to ICU, and mortality, while asthma was associated with a reduced risk of COVID-19 mortality. Patients with obesity were at a higher risk of experiencing severe symptoms of COVID-19 rather than mortality. Patients with cerebrovascular disease, chronic liver disease, chronic renal disease, or cancer were more likely to become severe COVID-19 cases and had a greater probability of mortality.Conclusions: COVID-19 patients with chronic diseases were more likely to experience severe symptoms and ICU admission and faced a higher risk of mortality. Aggressive strategies to combat the COVID-19 pandemic should target patients with chronic diseases as a priority.