Sulfotransferase 1C2 Increases Mitochondrial Respiration by Converting Mitochondrial Membrane Cholesterol to Cholesterol Sulfate.

Autor:	Kolb AJ; Department of Biology, School of Science, Indiana University-Indianapolis, Indianapolis, Indiana 46202, United States., Corridon P; Khalifa University of Science and Technology, P.O. Box 127788, Abu Dhabi, United Arab Emirates., Ullah M; Department of Anatomy, Cell Biology & Physiology, Indiana University School of Medicine, Indianapolis, Indiana 46202, United States., Pfaffenberger ZJ; Department of Chemistry, University of Michigan, Ann Arbor, Michigan 48109, United States., Xu WM; Division of Nephrology, Indiana Center for Biological Microscopy, Indiana University School of Medicine, Indianapolis, Indiana 46202, United States., Winfree S; Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska 68198, United States., Sandoval RH; Division of Nephrology, Indiana Center for Biological Microscopy, Indiana University School of Medicine, Indianapolis, Indiana 46202, United States., Hato T; Division of Nephrology, Indiana Center for Biological Microscopy, Indiana University School of Medicine, Indianapolis, Indiana 46202, United States., Witzmann FA; Department of Anatomy, Cell Biology & Physiology, Indiana University School of Medicine, Indianapolis, Indiana 46202, United States., Mohallem R; Department of Comparative Pathobiology, College of Veterinary Medicine, Bindley Bioscience Center, Purdue University, West Lafayette, Indiana 47907, United States., Franco J; IDEXX Laboratories, Westbrook, Maine 04092, United States., Aryal UK; Department of Comparative Pathobiology, College of Veterinary Medicine, Bindley Bioscience Center, Purdue University, West Lafayette, Indiana 47907, United States.; Purdue Proteomics Facility, Bindley Biosciences Center, Purdue University, West Lafayette, Indiana 47907, United States., Atkinson SJ; Department of Neuroscience, Physiology and Behavior, University of California, Davis, California 95616, United States., Basile DP; Department of Anatomy, Cell Biology & Physiology, Indiana University School of Medicine, Indianapolis, Indiana 46202, United States., Bacallao RL; Division of Nephrology, Indiana Center for Biological Microscopy, Indiana University School of Medicine, Indianapolis, Indiana 46202, United States.; Division of Nephrology, Richard Roudebush VA Medical Center, Indianapolis, Indiana 46202, United States.
Jazyk:	angličtina
Zdroj:	Biochemistry [Biochemistry] 2024 Sep 17; Vol. 63 (18), pp. 2310-2322. Date of Electronic Publication: 2024 Aug 28.
DOI:	10.1021/acs.biochem.3c00344
Abstrakt:	Hypothesis: In this communication, we test the hypothesis that sulfotransferase 1C2 (SULT1C2, UniProt accession no. Q9WUW8) can modulate mitochondrial respiration by increasing state-III respiration. Methods and Results: Using freshly isolated mitochondria, the addition of SULT1C2 and 3-phosphoadenosine 5 phosphosulfate (PAPS) results in an increased maximal respiratory capacity in response to the addition of succinate, ADP, and rotenone. Lipidomics and thin-layer chromatography of mitochondria treated with SULT1C2 and PAPS showed an increase in the level of cholesterol sulfate. Notably, adding cholesterol sulfate at nanomolar concentration to freshly isolated mitochondria also increases maximal respiratory capacity. In vivo studies utilizing gene delivery of SULT1C2 expression plasmids to kidneys result in increased mitochondrial membrane potential and confer resistance to ischemia/reperfusion injury. Mitochondria isolated from gene-transduced kidneys have elevated state-III respiration as compared with controls, thereby recapitulating results obtained with mitochondrial fractions treated with SULT1C2 and PAPS. Conclusion: SULT1C2 increases mitochondrial respiratory capacity by modifying cholesterol, resulting in increased membrane potential and maximal respiratory capacity. This finding uncovers a unique role of SULT1C2 in cellular physiology and extends the role of sulfotransferases in modulating cellular metabolism.
Databáze:	MEDLINE
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