Kolb 2024 Biochemistry
| Kolb AJ, Corridon P, Ullah M, Pfaffenberger ZJ, Xu WM, Winfree S, Sandoval RH, Hato T, Witzmann FA, Mohallem R, Franco J, Aryal UK, Atkinson SJ, Basile DP, Bacallao RL (2024) Sulfotransferase 1C2 increases mitochondrial respiration by converting mitochondrial membrane cholesterol to cholesterol sulfate. Biochemistry [Epub ahead of print]. https://doi.org/10.1021/acs.biochem.3c00344 |
Kolb Alexander J, Corridon Peter, Ullah Mahbub, Pfaffenberger Zechariah J, Xu Wei Min, Winfree Seth, Sandoval Ruben H, Hato Takeshi, Witzmann Frank A, Mohallem Rodrigo, Franco Jackeline, Aryal Uma K, Atkinson Simon J, Basile David P, Bacallao Robert L (2024) Biochemistry
Abstract: In this communication, we test the hypothesis that sulfotransferase 1C2 (SULT1C2, UniProt accession no. Q9WUW8) can modulate mitochondrial respiration by increasing state-III respiration.
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.
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.
• Bioblast editor: Plangger M
Labels: MiParea: Respiration
Stress:Ischemia-reperfusion Organism: Rat Tissue;cell: Kidney Preparation: Isolated mitochondria
Coupling state: LEAK, OXPHOS
Pathway: N, S, NS
HRR: Oxygraph-2k
2024-08
