# Mitochondria Functions Modified by Sulfotransferase 1C2

> **NIH VA I01** · RLR VA MEDICAL CENTER · 2020 · —

## Abstract

Acute kidney injury (AKI) is the most common renal disease requiring hospitalization and is associated with
significant mortality. There remains no reliable treatment modality for acute kidney injury. In the setting of
ischemia or hypoxic injury, early alterations in mitochondrial structure impair cellular energetics, activate cell
death pathways, increase oxygen free radical generation and may influence renal hemodynamics. Different
models of naturally or experimentally induced resistance to ischemic injury may help to identify biochemical,
cellular and physiological events underlying the injury process and provide potential targets for therapeutic
intervention. Our prior work uncovered a unique, unanticipated role for sulfotransferase 1C2 (SULT1C2) in
changing mitochondria physiology to confer protection against ischemic injury. Since we found SULT1C2 is
highly up-regulated in proteomic screens of mitochondria isolated from ischemia-preconditioned kidneys, we
tested whether kidneys transduced with plasmids bearing SULT1C2 are resistant to ischemia preconditioning.
The goal of this proposal is to delineate the extent of the contribution that SULT1C2 makes to altered cell
metabolism resulting in an ischemia preconditioned state. We will test the hypothesis that the mitochondria
adaptation due to ischemia preconditioning is due in part to direct action of sulfotransferase 1C2 on
mitochondria function brought about by changing cholesterol sulfate levels in mitochondria membranes.
In these studies, we will utilize two different models of resistance to AKI; 1) a genetic model of the Brown
Norway rat and Brown Norway derived consomic strains of rats, and 2) a model of experimentally induced
ischemic preconditioning. Studies in specific objective 1 will test the hypothesis that sulfotransferase 1C2
changes mitochondria respirome composition and physiology due to changes in membrane lipid organization.
These experiments will utilize a proteomic approach of label-free-quantitative mass spectroscopy to identify
biochemical similarities in different models of resistance. Specific aim 2 will test the hypothesis that
sulfotransferase 1C2 requires mitochondria receptors to convert cholesterol to cholesterol sulfate. Lastly aim 3
will test the hypothesis that inhibition of sulfotransferase 1C2 or down-regulation of sulfotransferase 1C2
markedly attenuates cellular protection against ischemia reperfusion injury. These studies will investigate post-
ischemic mitochondria respiratory capacity, mitochondrial polarization, renal hemodynamics and renal function
protection. Overall, the proposed studies will help provide an understanding of cytoprotective strategies and
identify potential therapeutic targets to manage the severity of AKI.

## Key facts

- **NIH application ID:** 10016916
- **Project number:** 1I01BX005184-01
- **Recipient organization:** RLR VA MEDICAL CENTER
- **Principal Investigator:** ROBERT L BACALLAO
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2020-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10016916

## Citation

> US National Institutes of Health, RePORTER application 10016916, Mitochondria Functions Modified by Sulfotransferase 1C2 (1I01BX005184-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10016916. Licensed CC0.

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