Sepsis restructures the mitochondrial calcium uniporter complex in the lymphoid tissues of mice and humans

Survivors of sepsis suffer from an elevated risk of premature death that is not explained by a higher burden of chronic diseases prior to the infection. Nearly 1 out of 4 survivors have persistent elevations of inflammation biomarkers, such as interleukin (IL) 6. These observations suggest that sepsis imparts durable changes to organismal biology. Eukaryotic life depends upon ATP and calcium (Ca2+). During sepsis, mitochondrial dysfunction, a failure of Ca2+ homeostasis, and sustained elevations in cytosolic [Ca2+] occur. These insults may serve as sufficient pressure to select for cells uniquely able to adapt. In this study, we compare the spleen and bone marrow lymphoid tissues of murine and human survivors of intraabdominal sepsis and non-sepsis critical illness (i.e., sterile trauma). We observe that sepsis induces in lymphoid tissues a restructuring of the mitochondrial calcium uniporter (MCU) complex: the critical channel mediating the electrophoretic uptake of Ca2+ into the mitoc..., , # Sepsis restructures the mitochondrial calcium uniporter complex in the lymphoid tissues of mice and humans

Dataset DOI: [10.5061/dryad.573n5tbkz](10.5061/dryad.573n5tbkz)

## Description of the data and file structure

We compared the lymphoid tissues (i.e., spleen, bone marrow) of mice that had survived to 7, 30, and 60 days days after either 1) cecal ligation puncture (CLP) followed by best clinical practices (i.e., control of the source of infection, resuscitation with balance crystalloids, 96 hours of antibiotics for the treatment of intraabdominal sepsis (CLP30d) or 2) sham laparotomy plus best clinical practices (Sham30d).

We performed the following analyses of tissue:

1. plasma cytokine concentrations by ELISA
2. protein expression of components of the mitochondrial calcium uniporter (MCU) complex
3. RT-PCR of components of the MCU complex
4. protein expression of pyruvate dehydrogenase E1alpha
5. concentrations of NAD+, NADH, NADtotal, and ATP
6. expression of cleaved casp..., The human subject study was approved by the Institutional Review Board (PRO#119120152). Written informed consent was obtained from all patients prior to inclusion. All ethical regulations relevant to human research participants were followed.